title: Normal induction but attenuated progression of germinal center responses in BAFF and BAFF-R signaling-deficient mice.
abstract: The factors regulating germinal center (GC) B cell fate are poorly understood. Recent studies have defined a crucial role for the B cell-activating factor belonging to TNF family (BAFF; also called BLyS) in promoting primary B cell survival and development. A role for this cytokine in antigen-driven B cell responses has been suggested but current data in this regard are limited. A BAFF receptor expressed by B cells (BAFF-R/BR3) is defective in A/WySnJ mice which exhibit a phenotype similar to BAFF-deficient (BAFF-/-) animals. Here, we show that although GC responses can be efficiently induced in both A/WySnJ and BAFF-/- mice, these responses are not sustained. In BAFF-/- mice, this response is rapidly attenuated and accompanied by perturbed follicular dendritic cell development and immune complex trapping. In contrast, analysis of the A/WySnJ GC response revealed a B cell autonomous proliferative defect associated with reduced or undetectable Ki67 nuclear proliferation antigen expression by GC B cells at all stages of the response. These data demonstrate a multifaceted role for the BAFF pathway in regulating GC progression.
authors.affiliation: Department of Microbiology and Immunology, and The Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19017-5541, USA.
authors.forename: Ziaur S M
authors.initials: ZS
authors.lastname: Rahman
authors.forename: Sambasiva P
authors.initials: SP
authors.lastname: Rao
authors.forename: Susan L
authors.initials: SL
authors.lastname: Kalled
authors.forename: Tim
authors.initials: T
authors.lastname: Manser
mesh_terms: D000818:Animals; D017209:Apoptosis; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002454:Cell Differentiation; D018858:Germinal Center / Q000276:immunology*; D019394:Ki-67 Antigen / Q000032:analysis; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha