Preferential usage of JH-proximal VH genes has been demonstrated in immature murine B cell repertoires. To determine whether this phenomenon is also evident in human repertoires, we studied utilization of VH6, the most JH-proximal human VH gene. Examination of VH gene usage in a panel of precursor B cell acute lymphoblastic leukemia samples indicated that 15% of the IgH rearrangements utilized VH6. VH6 is a single-member family in a total repertoire of 100-200 VH genes; thus, if usage were purely random, one would expect VH6 rearrangement frequency to be less than 1%. Analysis of VH gene usage in normal lymphoid tissues also revealed biased usage of VH6. VH6 was preferentially utilized in 16- to 24-week-old fetal liver as compared to adult peripheral blood mononuclear cells or spleen. Possible implications of the conservation of preferential usage of JH-proximal genes in both immature murine and human repertoires are discussed.

Scandinavian Journal of ImmunologyVolume 31, Issue 1 p. 109-119 Augmentation by Cytochalasin B of Antigen Receptor-Mediated Activation of Normal and Malignant Human B Lymphocytes L. SALTZ, L. SALTZ The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USASearch for more papers by this authorD. M. KNOWLES, D. M. KNOWLES The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USASearch for more papers by this authorS. MECHANIC, S. MECHANIC The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USASearch for more papers by this authorP. PASLEY, P. PASLEY The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USASearch for more papers by this authorR. BROOKS, R. BROOKS The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USASearch for more papers by this authorM. WAKAI, M. WAKAI The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USASearch for more papers by this authorN. CHIORAZZI, Corresponding Author N. CHIORAZZI The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USANicholas Chiorazzi, MD, Division of Rheumatology and Clinical Immunology, Department of Medicine, North Shore University Hospital, 300 Community Drive. Manhasset, New York 11030, USASearch for more papers by this author L. SALTZ, L. SALTZ The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USASearch for more papers by this authorD. M. KNOWLES, D. M. KNOWLES The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USASearch for more papers by this authorS. MECHANIC, S. MECHANIC The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USASearch for more papers by this authorP. PASLEY, P. PASLEY The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USASearch for more papers by this authorR. BROOKS, R. BROOKS The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USASearch for more papers by this authorM. WAKAI, M. WAKAI The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USASearch for more papers by this authorN. CHIORAZZI, Corresponding Author N. CHIORAZZI The Laboratory of Immunology, The Rockefeller University New York; The Departments of Medicine, North Shore University Hospital, Manhasset; Cornell University Medical College, New York; and The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, USANicholas Chiorazzi, MD, Division of Rheumatology and Clinical Immunology, Department of Medicine, North Shore University Hospital, 300 Community Drive. Manhasset, New York 11030, USASearch for more papers by this author First published: January 1990 https://doi.org/10.1111/j.1365-3083.1990.tb02749.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Baeker, T.R., Simms, E.R. & Rothstein, T.L. Cytochalasin induces an increase in cytosolic free calcium in murine B lymphocytes. J. Immunol. 138, 2691, 1987. 2 Bigler, R.D., Posnett, D.N. & Chiorazzi, N. Stimulation of a subset of normal resting T lymphocytes by a monoclonal antibody to a crossreactive determinant of the human T cell antigen receptor. J. Exp. Med. 161, 1450, 1985. 3 Braun, J., Hochman, P.S. & Unanue, E.R. Ligand induced association of surface immunoglobulin with the detergent–insoluble cytoskeletal matrix of the B lymphocyte. J. Immunol. 128, 1198, 1982. 4 Chiorazzi, N., Fu, S.M. & Kunkel, H.G. Stimulation of human B lymphocytes by antibodies to IgM and IgG: functional evidence for the expression of IgG on B lymphocyte surface membranes. Clin. Immunol. Immunopathol. 15, 301, 1980. 5 Cooper, M.D., Kearney, J.F., Gathings, W.E. & Lawton, A.R. Effects of anti–Ig antibodies on the development and differentiation of B cells. Immunol. Rev. 52, 29, 1980. 6 DeFranco, A.L., Raveche, E.S., Asofsky, R. & Paul, W.E. Frequency of B lymphocytes responsive to anti–immunoglobulin. J. Exp. Med. 155, 1523, 1982. 7 Flanagan, M.D. & Lin, S. Cytochalasins block actin filament elongation by binding to high affinity sites associated with F–actin. J. Biol. Chem. 255, 835, 1980. 8 Fothergill, J.J., Wistar, R., Woody, J.N. & Parker, D.C. A mitogen for human B cells: anti–Ig coupled to polyacrylamide beads activates blood mononuclear cells independently of T cells. J. Immunol. 128, 1945, 1982. 9 Fu, S.M., Chiorazzi, N. & Kunkel, H.G. Differentiation capacity and other properties of the leukemic cells of chronic lymphocytic leukemia. Immunol. Rev. 48, 23, 1980. 10 Hivroz, C., Grillot-Courvalin, C., Brouet, J. & Seligmann, M. Heterogeneity of responsiveness of chronic lymphocytic leukemia B cells to B cell growth factor or interleukin 2. Eur. J. Immunol. 16, 1001, 1986. 11 Hoffman, R., Ferguson, R. & Simms, R.L. Effect of cytochalasin B on human lymphocytic responses lo mitogens. Time and concentration dependence. J. Immunol. 118, 1472, 1977. 12 Howard, M., Farrar, J., Hilfiker, M., Johnson, B., Takatsu, K., Toshiyuki, M. & Paul, W.E. Identification of a T cell–derived B cell growth factor distinct from interleukin 2. J. Exp. Med. 155, 914, 1982. 13 Hume, D.A., Hansen, K., Weideman, M.J. & Ferber, E. Cytochalasin B inhibits lymphocyte transformation through its effects on glucose transport. Nature 272, 359, 1978. 14 Julius, B.H., Hensser, C.H. & Hartmann, E. Induction of resting B cells to DNA synthesis by soluble monoclonal anti–immunoglobulin. Eur. J. Immunol. 14, 753, 1984. 15 Kehrl, J.H., Muraguchi, A. & Fauci, A.S. Human B cell activation and cell cycle progression: stimulation with anti–mu and Staphylococcal aureus Cowen strain I. Eur. J Immunol. 14, 115, 1984. 16 Kishimoto, T., Miyake, T., Nishizawa, Y., Watanabe, T. & Yamamura, Y. Triggering mechanisms of B lymphocytes. I. Effect antiimmunoglobulin and enhancing soluble factors on differentiation and proliferation of B cells. J. Immunol. 115, 1179, 1975. 17 MacDougall, S.L., Grinstein, S. & Gelfand, E.W. Activation of Ca2+–dependent K+ channels in human B lymphocytes by anti–immunoglobulin. J. Clin. Invest. 81, 449, 1988. 18 MacLean-Gletcher, S. & Pollard, T.D. Mechanism of action of cytochalasin B on actin. Cell 20, 329, 1980. 19 Möller, G. B cell growth and differentiation factors. Immunol. Rev. 78, 1, 1984. 20 Mongini, P., Friedman, S. & Wortis, H. Accessory cell requirements for anti–IgM–induced proliferation of B lymphocytes. Nature 276, 709, 1978. 21 Monroe, J.G. & Cambier, J.C. B cell activation. I. Anti–immunoglobulin–induced receptor cross–linking results in a decrease in the plasma membrane potential of murine B lymphocytes. J. Exp. Med. 157, 2073, 1983. 22 Montazeri, G., Chiorazzi, N., Fu, S.M. & Kunkel, H.G. Regulatory role of circulating monocytes in the differentiative and proliferative responses of human B lymphocytes. Clin. Immunol. Immunopathol. 16, 1, 1980. 23 Mookerjee, B.K., Cuppoletti, J., Rampal, A.L. & Jung, C.Y. The effects of cytochalasins on lymphocytes. Identification of distinct cytochalasin binding sites in relation to mitogenic response and hexose transport. J. Biol. Chem. 256, 1290, 1981. 24 Muraguchi, A., Butler, J.L., Kehrl, J.M. & Fauci, A.S. Differential sensitivity of human B cell subsets to activation signals delivered by anti–IgM antibody and proliferative signals delivered by a monoclonal B cell growth factor. J. Exp. Med. 157, 530, 1983. 25 Muraguchi, A., Kehrl, J.M., Butler, J.L. & Fauci, A.S. Sequential requirements for cell cycle progression of resting human B cells after activation by anti– Ig. J. Immunol. 132, 176, 1984. 26 Philips, N.E. & Parker, D.C. Fc–dependent inhibition of mouse B cell activation by whole anti–mu antibodies. J. Immunol. 130, 602, 1983. 27 Rothstein, T.L. Anti–immunoglobulin in combination with cytochalasin stimulates proliferation of murine B lymphocytes, J. Immunol. 135, 106, 1985. 28 Rothstein, T. L. Stimulation of B cells by sequential addition of anti–immunoglobulin antibody and cytochalasin. J. Immunol. 136, 813, 1986. 29 Rudich, S.M., Winchester, R. & Mongini, P.K.A. Human B cell activation: evidence for diverse signals provided by various monoclonal anti–IgM antibodies. J. Exp. Med. 162, 1236, 1985. 30 Sell, S. & Gell, P.G.M. Studies on rabbit lymphocytes in vitro. I. Stimulation of blast transformation with an antiallotype serum. J. Exp. Med. 122, 423, 1965. 31 Sidman, C.L. & Unanue, E.R. Requirements for mitogenic stimulation of murine B cells by soluble anti–IgM antibodies. J. Immunol. 122, 406, 1979. 32 Sieckmann, D.G., Asofsky, R., Mosier, D.E., Zitron, I.M. & Paul, W.E. Activation of mouse lymphocytes by anti–Ig. I. Parameters of the proli–ferative response. J. Exp. Med. 147, 814, 1978. 33 Weiner, M.L., Moorhead, J.W., Yamaga, K. & Kubo, R.T. Anti–immunoglobulin stimulation and requirements for cross–linkage. J. Immunol. 117, 1527, 1976. 34 Wessels, N.K., Spooner, B.S., Ash, J.F., Bradley, M.O., Luduena, M.A., Taylor, E.L., Wrenn, J.T. & Yamada, K.M. Microfilaments in cellular and developmental processes. Science 171, 135, 1971. 35 Valentine, M.A. & Vaughn, J.A. Augmentation of interleukin–2 release by cytochalasins. Cell. Inmmnol. 101, 651, 1986. 36 Yoshinaga, M., Yoshinaga, A. & Waksman, B. Regulation of lymphocyte responses in vitro: potentiation and inhibition of rat lymphocyte responses to antigen and mitogens by cytochalasin B. Proc. Natl. Acad. Sci. USA 69, 3251, 1972. Citing Literature Volume31, Issue1January 1990Pages 109-119 ReferencesRelatedInformation

A cytoplasmic glycoprotein, originally identified by the monoclonal antibody 465.12S in melanoma tumors, is significantly increased in epithelial cells of different histotype following transformation. In the present study we show that the cytoplasmic melanoma associated antigen (cyt-MAA) is drastically enhanced in lymphoid cells by polyclonal and allogeneic stimulation, as well as by transformation. Normal T-cells with helper and suppressor phenotype are far more susceptible than B-cells to this enhancement. However, among transformed lymphoid cells, the expression of the cyt-MAA does not correlate with lineage, but rather with stage of differentiation. Acute lymphoblastic leukemias represent the only exception, since in these lymphoid malignancies cyt-MAA levels are highly heterogeneous even within groups of phenotypically similar lesions. Thus, the expression of the cyt-MAA is shared by cells of distant embryological origin in early stages of their differentiation and/or during proliferation. Quantitation of the cyt-MAA may provide useful information for the classification of some lymphoid malignancies.

Journal Article AIDS: A Disease Confronting the Clinical Laboratory Get access Daniel M. Knowles, MD Daniel M. Knowles, MD Immunopathology Laboratory, Department of Pathology, and the Kaplan Cancer Center, New York University School of Medicine, New York, NY 10016. Search for other works by this author on: Oxford Academic PubMed Google Scholar Laboratory Medicine, Volume 17, Issue 11, 1 November 1986, Pages 657–658, https://doi.org/10.1093/labmed/17.11.657 Published: 01 November 1986

We report in this paper the generation and characterization of three monoclonal antibodies, designated alpha BL1, alpha BL2, and alpha BL3, that recognize distinctive antigens unrelated to complement, Fc, and mouse erythrocyte rosette receptors, which are preferentially expressed on B lymphocytes. alpha BL1 recognizes a heat stable nonimmunoprecipitable antigen, possibly glycolipid in nature. Alpha BL2 recognizes a nonreducible single polypeptide with a m.w. of 68,000 that occasionally co-precipitates with a p29,34 complex of HLA-DR antigens. Alpha BL3 recognizes a nonreducible single polypeptide with a m.w. of 105,000 with an acidic pI point. We demonstrated that BL1 is expressed on fetal liver hematopoietic cells, a small subset (5 to 15%) of Ficoll-Hypaque-separated normal bone marrow cells, and on a subpopulation of nonadherent, non-E rosette-forming cells and granulocytes. BL2 is expressed on fetal liver hematopoietic cells, on 3 to 7% of normal bone marrow cells, and on a majority (40 to 70%) of nonadherent, non-E rosette-forming cells with a distinctive pattern similar to that of HLA-DR. BL3 is expressed on a subpopulation of nonadherent, non-E rosette-forming cells, and on occasional cells in the monocyte-enriched adherent cell population. The peak fluorescence for BL2 is substantially higher than that of BL1 and BL3, indicating higher BL2 antigen density. All three antigens are absent from thymocytes and E rosette-positive T cell fractions obtained from various lymphoid tissues. Cellular distribution of the BL antigens on various well-characterized established hematopoietic cell lines, leukemias, and malignant lymphomas, in conjunction with the results of the in vitro activation and TPA-induction experiments, suggest that BL1 is expressed during early developmental stages of B cell differentiation, whereas BL3 is expressed at the later stages. BL2 expression spans immature and mature stages of B cell differentiation, with the exception of mature plasma cells. The alpha BL antibodies described here should prove to be useful in the investigation of B cell differentiation and in the clinical diagnosis of lymphoid neoplasms.

A series of six monoclonal antibodies reactive with hematopoietic differentiation antigens expressed at different stages of myelocytic and erythrocytic differentiation have been developed. One of these antibodies (IG10) is reactive mainly with mature and immature granulocytes, including CFU-GM. Four of these antibodies (T5A7, T3A3, L4F3, L182) are reactive with both granulocytes and monocytes and can be used to define distinct stages in granulocytic maturation. All are reactive with CFU-GM. The sixth antibody (5F1) is reactive with monocytic and nucleated erythrocytic elements, including CFU-E. Of particular interest is the observation that antibody 5F1 in the absence of complement inhibits CFU-E growth. None of these antibodies react with peripheral blood or bone marrow lymphocytes, thymocytes or erythrocytes. Potential use of such reagents in studies of normal and malignant hematopoietic differentiation will be discussed.

Extracardiac rhabdomyomas are rare benign neoplasms that in the past have been divided by histologic criteria into adult and fetal types. In this series, 15 previously unpublished cases are presented and analyzed in combination with 51 acceptable cases from the literature. The adult type of rhabdomyoma occurs almost exclusively in the head and neck region (93% of all cases), particularly in the larynx and pharynx of adult males. The fetal type of rhabdomyoma may be subdivided on histologic grounds into myxoid and cellular variants. The fetal myxoid type usually occurs in the vulvovaginal region of middle aged women or in the postauricular region of male infants. The fetal cellular type has not been previously emphasized. This type tends to occur in the head and neck region of adult males. It may be mistaken for a sarcoma because of its high degree of cellularity. Local recurrence of a rhabdomyoma is rare and has only been occasionally reported in the adult type of rhabdomyoma. In no instance has a rhabdomyoma been shown to possess aggressive local growth or metastatic potential. Therefore, it is essential that these neoplasms be recognized histologically and that they be treated conservatively by local excision.

In response to an article on hepatic cell adenomas and oral contraceptives it is argued that there is a histopathologic differentiation of FNH (focal nodular hyperplasia) from liver cell adenoma. FNH shows a central stellate scar with proliferating intranodular and internodular bile ductules. Some characteristics of described liver cell adenoma are features of FNH as reflected by normal liver scans and absence of rupture and hemorrhage. Hepatic cell adenomas are not well documented and because of lack of precision in diagnosing FNH from liver cell adenomas there is confusion in reports. FNH rarely ruptures or hemorrhages and the association between FNH and oral contraceptives is unclear as children have FNH lesions.

The patient described here had a nodular, poorly differentiated lymphocytic lymphoma associated with a serum monoclonal protein, IgG lambda. Following a three year period of radiation-induced clinical remission she developed generalized diffuse histiocytic lymphoma. Direct immunoperoxidase staining of the tissue sections demonstrated that the neoplastic cells of each biopsy only contained IgG lambda immunoglobulin, identical to the serum monoclonal protein. This is presumptive evidence that these two histopathologically distinctive malignant lymphomas, occurring consecutively in the same patient, were responsible for the synthesis and secretion of the same serum M component. This strongly suggests that both lymphoid neoplasms arose from the same malignant clone. The results 1) confirm the light microscopic observation that nodular lymphocytic lymphoma may progress to diffuse histiocytic lymphoma and 2) offer further evidence that histiocytic lymphomas arising in patients with previous B cell malignancies are most probably related to the original B cell proliferation and do not represent the emergence of a second, separate malignant clone.

Pleomorphic reticulum cell sarcoma, a histologic variant of the histiocytic lymphomas, presented as an abdominal mass in a 52-year-old woman. Extensive amyloid deposition was present within the tumor mass and an M-component (IgG Lambda) was identified in the serum. Direct immunoperoxidase staining of tissue sections demonstrated the same monoclonal immunoglobulin to be present within the neoplastic cells, presumptive evidence of their ability to both synthesize and secrete immunoglobulin. The presence of amyloid within this patient was probably the direct result of the tissue deposition of this monoclonal immunoglobulin and may be related to the amyloidogenic nature of Lambda light chains. Immunoglobulin production is a specific property of the B lymphocyte series. Transforming B lymphocytes and their differentiating progeny are engaged in active immunoglobulin synthesis and thus may be distinguished from morphologically identical but functionally distinct cells. The demonstration of cytoplasmic monoclonal immunoglobulin within these “malignant reticulum cells” strongly supports the assertion that at least some “histiocytic lymphomas” are neoplastic analogues of transformed B lymphocytes, and are not derived from phagocytic histiocytes, as previously believed.

KNOWLES, DANIEL M. II M.D.; CASARELLA, WILLIAM J. M.D.; JOHNSON, PHILIP M. M.D.; WOLFF, MARIANNE M.D. Author Information

A case of epithelial thymoma occurring synchronously with Philadelphia chromosome-positive chronic myelogenous leukemia and urinary bladder carcinoma in a 76-year-old man is described. Thymomas have been associated with numberous hematologic, collagen-vascular and autoimmune disease states, as well as with an increased incidence of nonthymic malignancy. Human thymoma-associated leukemia is, however, extremely unusual, despite the well-documented role of the thymus in leukemogenesis in experimental animals. No previous literature reports of thymoma associated with chronic myelogeneous leukemia were found. A review of long-term followup data of surviving thymoma patients is necessary to determine if an increased propensity to develop leukemia is present in present in patients with thymoma.