Bcmd decreases the life span of B-2 but not B-1 cells in A/WySnJ mice.
Peripheral B cells are divided into two subpopulations, B-1 and B-2, the relationship of which remains obscure. We recently showed that the Bcmd mutation in A/WySnJ mice reduces average B cell life span, yielding 90% fewer peripheral B cells. Despite this defect, A/WySnJ mice have an elevated proportion of peritoneal CD5+ B cells, suggesting that Bcmd may be the first B-cell-intrinsic gene to differentially affect the B-1 and B-2 subpopulations. To test this hypothesis in detail, we have used in vivo BrdU labeling and four-color cytofluorometry to examine the numbers and turnover rates of sIgM+CD23-CD43+ (B-1) and sIgM+CD23+CD43- (B-2) splenocytes in A/WySnJ and A/J mice. The results show the expected 90% reduction of splenic B-2 cells among A/WySnJ mice, but a normal splenic B-1 cell pool. Increased B-1 cell renewal cannot explain this undiminished pool, because BrdU labeling kinetics reveals an identical splenic B-1 subset turnover rate of approximately 4%/day in both A/WySnJ and A/J strains. Thus, B-1 cells are Bcmd-independent but B-2 cells are Bcmd-dependent, suggesting Bcmd functions in a positive signaling pathway that imparts longevity to quiescent B cells, but that is not required for cycling B cells. Moreover these results show that the requisites for maturation and longevity differ between the B-1 and B-2 subsets.
Lentz
V M
VM
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Hayes
C E
CE
Cancro
M P
MP
D000818:Animals; D015703:Antigens, CD; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D016922:Cellular Senescence / Q000235:genetics* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000378:metabolism; D007700:Kinetics; D051917:Leukosialin; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008817:Mice, Mutant Strains; D009154:Mutation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology
D015703:Antigens, CD; D007075:Immunoglobulin M; D051917:Leukosialin; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D001973:Bromodeoxyuridine