title: Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cells.
abstract: In primary humoral responses, B-cell lymphoma 6 (Bcl6) is a master regulator of follicular helper T (TFH) cell differentiation; however, its activation mechanisms and role in memory responses remain unclear. Here we demonstrate that survival of CXCR5(+) TFH memory cells, and thus subsequent recall antibody response, require Bcl6 expression. Furthermore, we show that, upon rechallenge with soluble antigen Bcl6 in memory TFH cells is rapidly induced in a dendritic cell-independent manner and that peptide:class II complexes (pMHC) on cognate memory B cells significantly contribute to this induction. Given the previous evidence that antigen-specific B cells residing in the follicles acquire antigens within minutes of injection, our results suggest that memory B cells present antigens to the cognate TFH memory cells, thereby contributing to rapid Bcl6 reexpression and differentiation of the TFH memory cells during humoral memory responses.
authors: Laboratory of Lymphocyte Differentiation, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan;
authors: Wataru
authors: W
authors: Ise
authors: Laboratory of Lymphocyte Differentiation, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan;
authors: Takeshi
authors: T
authors: Inoue
authors: Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112;
authors: James B
authors: JB
authors: McLachlan
authors: Laboratory for Lymphocyte Differentiation.
authors: Kohei
authors: K
authors: Kometani
authors: Laboratory for Cytokine Regulation, andDivision of Molecular Pathology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda-shi, Chiba 278-0022, Japan.
authors: Masato
authors: M
authors: Kubo
authors: Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; and.
authors: Takaharu
authors: T
authors: Okada
authors: Laboratory of Lymphocyte Differentiation, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan;Laboratory for Lymphocyte Differentiation, kurosaki@ifrec.osaka-u.ac.jp.
authors: Tomohiro
authors: T
authors: Kurosaki
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000378:metabolism; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: C490010:Bcl6 protein, mouse; C513179:CXCR5 protein, mouse; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5
keywords: antibody production; immunological memory