Crucial role for BAFF-BAFF-R signaling in the survival and maintenance of mature B cells

• Published in: PloS one Vol. 4; no. 5; p. e5456
• Main Authors: Rauch, Melanie, Tussiwand, Roxane, Bosco, Nabil, Rolink, Antonius G
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06-05-2009; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - pharmacology; Apoptosis; B cells; B-1 cells; B-Cell Activating Factor - metabolism; B-Cell Activation Factor Receptor - metabolism; B-Lymphocytes - cytology; B-Lymphocytes - metabolism; Binding; Biocompatibility; BLyS protein; Bone marrow; Cell Differentiation; Cell size; Cell survival; Cell Survival - physiology; Cells, Cultured; Complement system; Cytotoxicity; Depletion; Drosophila; Female; Flow Cytometry; Follicles; Immune response; Immune response (humoral); Immune system; Immunization; Immunoenzyme Techniques; Immunoglobulins; Immunological memory; Immunology; Immunology/Autoimmunity; Immunology/Leukocyte Development; Injection; Insects; Leukemia; Lupus; Lymphocyte receptors; Lymphocytes; Lymphocytes B; Lymphocytes T; Lysis; Maintenance; Memory cells; Mice; Mice, Inbred C57BL; Mice, Transgenic; Monoclonal antibodies; Multiple myeloma; Proteins; Proto-Oncogene Proteins c-bcl-2 - physiology; Rats; Rats, Inbred Lew; Rodents; Spleen - immunology; Spleen - metabolism; Survival; T cells; Toxicity; Transgenic animals; Viral antibodies
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0005456

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.