B Cell and T Cell Dissimilarities in BAFF-Deficient versus BR3-Deficient C57BL/6 Mice

BAFF is a potent B cell survival and differentiation factor with three receptors, TACI, BCMA, and BR3. B cells are greatly reduced in BAFF-deficient mice, and among mice deficient in a single BAFF receptor, B cell reduction is characteristic only of BR3-deficient mice. Nevertheless, there may be important differences between BR3-deficient mice, in which interactions between BAFF and only BR3 are abrogated, and BAFF-deficient mice, in which interactions between BAFF and all its receptors are abrogated. We demonstrate that: 1) the numbers of CD19+ cells in C57BL/6 (B6).Baff-/- and B6.Br3-/- mice diverge as the mice age; 2) the distribution of B cell subsets significantly differ between B6.Baff-/- and B6.Br3-/- mice regardless of age or sex; 3) the relationships of CD3+ and CD4+ cells to B cells vastly differ between B6.Baff-/- and B6.Br3-/- mice as a function of age and sex; 4) the numbers and percentages of CD4+Foxp3+ and CD4+CD25+Foxp3+ are greater in B6.Baff-/- mice than in B6.Br3-/- mice; and 5) for any given number of CD19+ cells or CD4+ cells, percentages of Foxp3+ cells and CD4+CD25+Foxp3+ cells are lower in B6.Br3-/- mice than in B6.Baff-/- mice, with proliferation of these cells being greater, and survival being lesser, in B6.Br3-/- mice than in B6.Baff-/- mice. Collectively, these observations raise the possibility that interactions between TACI and/or BCMA and BAFF modulate expression of B cell subsets and Foxp3+ cells and may help explain prior enigmatic observations of autoimmunity and autoimmune disease in mice despite the absence of functional engagement of BR3 by BAFF.