B Cells With Complementary B Cell Receptors Can Kill Each Other.

B cells differentiate from hematopoietic stem cells in the bone marrow (BM) and migrate as transitional cells to the spleen where final maturation takes place. Due to the enormous diversity in variable (V) regions of B cell receptors for antigen (BCR), B cells with complementary BCRs are likely to be generated. These could encounter each other in the BM or in secondary lymphoid organs. The outcome of such an event is unknown. To study this issue, we used two strains of gene-modified mice whose B cells display complementary BCRs. B cells of one strain express an idiotype⁺ (Id⁺) BCR while B cells of the other strain display an anti-idiotypic (αId) BCR. In vitro, B cells with complementary BCRs killed each other in a mechanism that required physical binding between BCR V-regions. In contrast, killing was unilateral in vivo: αId B cells with a follicular (FO) B cell phenotype were expanded, while Id⁺ B cells with a marginal zone (MZ) phenotype became deleted. The results show that B cells with complementary BCRs can recognize and regulate each other in vivo. This mechanism should be taken into account in theories for idiotypic regulation of the immune system.