Crucial role for BAFF-BAFF-R signaling in the survival and maintenance of mature B cells.
Defects in the expression of either BAFF (B cell activating factor) or BAFF-R impairs B cell development beyond the immature, transitional type-1 stage and thus, prevents the formation of follicular and marginal zone B cells, whereas B-1 B cells remain unaffected. The expression of BAFF-R on all mature B cells might suggest a role for BAFF-R signaling also for their in vivo maintenance. Here, we show that, 14 days following a single injection of an anti-BAFF-R mAb that prevents BAFF binding, both follicular and marginal zone B cell numbers are drastically reduced, whereas B-1 cells are not affected. Injection of control, isotype-matched but non-blocking anti-BAFF-R mAbs does not result in B cell depletion. We also show that this depletion is neither due to antibody-dependent cellular cytotoxicity nor to complement-mediated lysis. Moreover, prevention of BAFF binding leads to a decrease in the size of the B cell follicles, an impairment of a T cell dependent humoral immune response and a reduction in the formation of memory B cells. Collectively, these results establish a central role for BAFF-BAFF-R signaling in the in vivo survival and maintenance of both follicular and marginal zone B cell pools.
Developmental and Molecular Immunology, Department of Biomedicine (DBM), University of Basel, Basel, Switzerland.
Melanie
M
Rauch
Roxane
R
Tussiwand
Nabil
N
Bosco
Antonius G
AG
Rolink
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D053264:B-Cell Activating Factor / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D007114:Immunization; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D019253:Proto-Oncogene Proteins c-bcl-2; C486662:Tnfrsf13c protein, mouse