The influence of BCR density on the differentiation of natural poly-reactive B cells begins at an early stage of B cell development.

B cell antigen receptor (BCR) density plays a role in the differentiation of immature B cells to their mature compartments; however, the exact strategy of its influence on the development of natural autoreactive B cells is still unclear. In the present study, we explored the role of BCR surface density in autoreactive B cell development by studying two lines of mice containing distinct copy numbers of an IgH transgene with VH derived from a poly-reactive natural antibody 3B4. Surface BCR levels were found to be related to the transgene copy number in these mice. In mice with higher copy numbers of the transgene, the BCRs were found to promote the remaining of autoreactive B cells into marginal zone (MZ) and B-1a subsets; meanwhile, elevated surface BCR levels were correlated with a significant decrease of follicular (Fo) B cell numbers and a reduction in the number of multiple stages of immature B cells both in spleen and bone marrow (BM). Interestingly, no difference in the ratio of cell apoptosis and proliferation was found in all stages of B cell development between two lines, except that more severely aberrant proliferation of pro/pre-B cells in BM was found in mice with higher transgene copies. This data supports the idea that natural poly-reactive B cells can be positively selected into MZ and B-1 cells, and high BCR surface density favors this selection. More importantly, our data suggests that the influence by receptor expression on the differentiation of natural poly-reactive B cells begins at an early stage of B cell development.