crucial role for baff-baff-r signaling in the survival and maintenance of mature b cellsbaff-baff-r信号的关键作用的生存和维护成熟的b细胞.pdfVIP

Crucial Role for BAFF-BAFF-R Signaling in the Survival and Maintenance of Mature B Cells Melanie Rauch, Roxane Tussiwand, Nabil Bosco, Antonius G. Rolink* Developmental and Molecular Immunology, Department of Biomedicine (DBM), University of Basel, Basel, Switzerland Abstract 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. Citation: Rauch M, Tussiwand R, Bosco N, Rolink AG (2009) Crucial Role for BAFF-BAFF-R Signaling in the Survival and Maintenance of Mature B Cells. PLoS ONE 4(5): e5456. doi:10.1371/journal.pone.0005456 Editor: Wasif N. Khan, University of Miami, United States of America Received August 7, 2008; Accepted April 7, 2009; Published May 6, 2009 Copyright: 2009 Rauch