Bcmd governs recruitment of new B cells into the stable peripheral B cell pool in the A/WySnJ mouse.
The A/WySnJ mouse provides a genetic model for studying new B cell selection into the stable peripheral B cell pool. Unlike the related A/J strain, the A/WySnJ has a single, autosomal codominant gene defect, Bcmd, resulting in a profound peripheral B cell deficiency. Here, continuous in vivo bromodeoxyuridine labeling and immunofluorescence analysis showed normal bone marrow B cell genesis but excessive B cell loss from the marrow and each peripheral pool in A/WySnJ. The A/WySnJ immature B220low/HSAhigh splenic B cell pool was 79% smaller, had a 69% slower renewal rate, and its cells had a 29% shorter average half-life than A/J. The A/WySnJ mature B220high/HSAlow splenic B cell pool was 92% smaller, had an 83% slower renewal rate, and its cells had a 56% shorter average half-life. In reciprocal chimeras, the A/WySnJ marrow failed to repopulate the peripheral B cell pool in A/J mice, whereas the A/J marrow fully reconstituted the A/WySnJ mice. Histochemistry revealed disordered splenic architecture in A/WySnJ, with few primary lymphoid follicles and a second abnormal phenotype, mastocytosis. There was no common genetic basis for B cell deficiency and mastocytosis in the F2 progeny of an (A/WySnJ x CAST/Ei)F1 intercross. We conclude that Bcmd is expressed in bone marrow cells, most likely B cells, where it hinders short-lived B cell maturation to a long-lived phenotype with the potential to form memory B cells.
Lentz
V M
VM
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Cancro
M P
MP
Nashold
F E
FE
Hayes
C E
CE
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D008415:Mastocytosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D008817:Mice, Mutant Strains; D011828:Radiation Chimera / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology