title: BASH-deficient mice: limited primary repertoire and antibody formation, but sufficient affinity maturation and memory B cell generation, in anti-NP response.
abstract: Signaling through the B cell antigen receptor (BCR) induces activation and proliferation of B cells, a response that requires the adaptor protein BASH (also known as BLNK/SLP-65). Although BASH and other molecules, such as Btk, PLCgamma2 and PKCbeta, are known to be essential for T cell-independent immune responses in vivo, their requirement during T cell-dependent immune responses, especially their role in antibody affinity-maturation and memory B cell generation remains unclear. In this study, we examined primary and memory immune responses to the T cell-dependent hapten antigen, (4-hydroxy-3-nitrophenyl)acetyl (NP) conjugated to chicken gammaglobulin (CGG), in BASH-deficient mice on a C57BL/6 background. In the primary response, NP-specific IgM was barely produced and the typical anti-NP IgG1/lambda production was markedly attenuated, but kappa chain was unexpectedly over-represented in the anti-NP antibodies. In contrast, CGG-specific IgG1 was normally produced. In the memory response, IgG1/lambda antibody with high affinity to NP was produced at normal level in the mutant mice. The frequency and distribution of somatic mutations in the V(H)186.2 genes of the anti-NP IgG1/lambda antibody were also normal. These results indicate that BASH-mediated BCR signaling is dispensable for somatic hypermutation and affinity selection, as well as generation and response of memory B cells. Interestingly, mutated V(H) genes with the same clonal origin were prominent in the anti-NP antibodies of BASH-deficient mice, indicating that a limited number of original clones had been recruited into the memory compartment. Thus, the scarcity of specific clones in the primary repertoire and an impaired primary response is not detrimental to the quality and quantity of a memory response.
authors.affiliation: Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Nojima
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Ryo
authors.initials: R
authors.lastname: Goitsuka
authors.forename: Koji
authors.initials: K
authors.lastname: Furukawa
authors.forename: Takachika
authors.initials: T
authors.lastname: Azuma
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kitamura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D049109:Cell Proliferation; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics*; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009596:Nitrophenols / Q000276:immunology; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D009596:Nitrophenols; D010750:Phosphoproteins