title: Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation.
abstract: We have assessed the role of B lymphocyte stimulator (BLyS) and its receptors in the germinal center (GC) reaction and affinity maturation. Despite ample BLyS retention on B cells in follicular (FO) regions, the GC microenvironment lacks substantial BLyS. This reflects IL-21-mediated down-regulation of the BLyS receptor TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) on GC B cells, thus limiting their capacity for BLyS binding and retention. Within the GC, FO helper T cells (TFH cells) provide a local source of BLyS. Whereas T cell-derived BLyS is dispensable for normal GC cellularity and somatic hypermutation, it is required for the efficient selection of high affinity GC B cell clones. These findings suggest that during affinity maturation, high affinity clones rely on TFH-derived BLyS for their persistence.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Radhika
authors.initials: R
authors.lastname: Goenka
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Matthews
authors.forename: Bochao
authors.initials: B
authors.lastname: Zhang
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: O'Neill
authors.forename: Jean L
authors.initials: JL
authors.lastname: Scholz
authors.forename: Thi-Sau
authors.initials: TS
authors.lastname: Migone
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
authors.forename: William
authors.initials: W
authors.lastname: Stohl
authors.forename: Uri
authors.initials: U
authors.lastname: Hershberg
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cancro
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D000917:Antibody Formation / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D018858:Germinal Center / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*; D053303:Transmembrane Activator and CAML Interactor Protein / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; C486361:Tnfrsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein