Skewed B cell differentiation affects lymphoid organogenesis but not T cell-mediated autoimmunity.

B cell receptor ( BCR) signalling determines B cell differentiation and may potentially alter T cell-mediated immune responses. In this study we used two transgenic strains of BCR-deficient mice expressing Epstein-Barr virus latent membrane protein ( LMP)2 A in B cells, where either follicular and marginal zone differentiation ( D_HLMP2A mice) or B-1 cell development ( V_HLMP2A mice) were supported, and evaluated the effects of skewed B lymphocyte differentiation on lymphoid organogenesis and T cell responses in vivo. Compared to wild-type animals, both transgenic strains displayed alterations in the composition of lymphoid organs and in the dynamics of distinct immune cell subsets following immunization with the self-antigen PLP_185-206. However, ex-vivo T cell proliferation to PLP_185-206 peptide measured in immunized D_HLMP2A and V_HLMP2A mice was similar to that detected in immunized control mice. Further, clinical expression of experimental autoimmune encephalitis in both LMP2A strains was identical to that of wild-type mice. In conclusion, mice with skewed B cell differentiation driven by LMP2A expression in BCR-negative B cells do not show changes in the development of a T cell mediated disease model of autoimmunity, suggesting that compensatory mechanisms support the generation of T cell responses. [ABSTRACT FROM AUTHOR]