title: Two waves of memory B-cell generation in the primary immune response.
abstract: Memory B cells can be generated independently of germinal center (GC) formation and affinity maturation in Bcl-6-deficient mice, but the contribution of the GC-independent pathway for memory B-cell generation in normal mice remains unknown. To examine this, we administrated anti-inducible co-stimulator (ICOS) mAbs into mice at the onset of GC formation in the primary response. This manipulation affected the generation of GC B cells in the spleen, but neither IgG1 memory B cell nor production of IgG1 long-term antibody was affected. In ICOS-manipulated mice, GC B cells accumulated somatic mutations in the IgV(H) genes and underwent affinity maturation; however, memory B cells scarcely accumulated mutations and reconstituted the secondary response by low affinity, supporting the notion that low-affinity memory B cells are generated in a GC-independent manner. Thus, it appears that memory B cells are established by two different pathways, associated with or without GC reaction and affinity maturation. The generation and long-term persistence of low-affinity IgG1 memory B cells and antibodies in ICOS-manipulated mice support the idea that low-affinity memory B cells may give rise to long-term antibody-forming cells.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Inamine
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Nobue
authors.initials: N
authors.lastname: Baba
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miyake
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: Toshitada
authors.initials: T
authors.lastname: Takemori
authors.forename: Ryo
authors.initials: R
authors.lastname: Abe
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D018858:Germinal Center / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D060889:Inducible T-Cell Co-Stimulator Protein; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein