Bcmd governs recruitment of newly formed B-2 cells into the stable peripheral B cell pool

The A/WySnJ strain of mice harbors a single autosomal trait that causes profound B cell deficiency. The studies described herein further characterize Bcmd, and provide insight regarding the mechanisms involved in recruitment of cells to the long lived peripheral B cell pool. The results of cytofluorimetric and BrdU labeling studies show that Bcmd reduces peripheral B cell life span. In addition, reciprocal and mixed bone marrow chimeras were constructed, and demonstrate that Bcmd is an intrinsic B cell defect. Further, cytofluorimetric analysis coupled with in vitro TUNEL assays show that Bcmd results in an increased apoptotic death rate among peripheral B cells, suggesting it interferes with signals that normally avert programmed cell death. Finally, cytofluorimetric and BrdU labeling analyses of B-1 cells reveal they are unaffected by Bcmd, indicating that B-1 and B-2 cells differ in their requisites for maturation and longevity. These studies suggest that discrete events which mediate recruitment of transitional B cells into the long lived pool occur during late stages of peripheral B cell maturation. Further, they suggest that in the absence of these events, the default pathway is programmed cell death. Finally, since the shortened life span of mature A/WySnJ B cells affects neither primary humoral responses, initiation of germinal centers nor isotype switching, at least one determinant of B cell longevity is separable from antigen-driven processes