title: Modulation of Igβ is essential for the B cell selection in germinal center.
abstract: The positive and negative selection of antigen-reactive B cells take place in the germinal center (GC) during an immune responses. However, the precise molecular mechanisms underlying these selection machineries, including the involvement of antigen receptor signaling molecules, remain to be elucidated. We found that expression levels of Igα and Igβ, which are the essential components of B cell antigen-receptor complex, were differentially regulated in GC B cells and that the expression of Igβ was more prominently down-regulated in a portion of GC B cells. The suppression of Igβ down-regulation reduced the number of GL7(+)GC B cells and the affinity maturation in T-dependent responses was markedly impaired. In addition, the disease phenotypes in autoimmune-prone mice were ameliorated by blocking of Igβ down-regulation. These results suggest that Igβ down-regulation is involved in the normal positive selection in GC and the accumulation of autoreactive B cells in autoimmune-prone mice.
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University Yoshidakonoecho, Sakyoku, Kyoto 606-8501, Japan.
authors.forename: Kagefumi
authors.initials: K
authors.lastname: Todo
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University Yoshidakonoecho, Sakyoku, Kyoto 606-8501, Japan.
authors.forename: Orie
authors.initials: O
authors.lastname: Koga
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University Yoshidakonoecho, Sakyoku, Kyoto 606-8501, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University Yoshidakonoecho, Sakyoku, Kyoto 606-8501, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hikida
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051925:CD79 Antigens / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism*; D017578:Immunoglobulin Class Switching; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D027041:Somatic Hypermutation, Immunoglobulin; D000098546:Interleukin-21
chemical_list: D051925:CD79 Antigens; D007378:Interleukins; D000098546:Interleukin-21