BASH-deficient mice: Limited primary repertoire and antibody formation, but sufficient affinity maturation and memory B cell generation, in anti-NP response

Mutsumi Yamamoto, Takuya Nojima, Katsuhiko Hayashi, Ryo Goitsuka, Koji Furukawa, Takachika Azuma, Daisuke Kitamura

Research output: Contribution to journalArticle

8 Citations (Scopus)

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, PLCγ2 and PKCβ, 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/λ production was markedly attenuated, but κ chain was unexpectedly overrepresented in the anti-NP antibodies. In contrast, CGG-specific IgG1 was normally produced. In the memory response, IgG1/λ antibody with high affinity to NP was produced at normal level in the mutant mice. The frequency and distribution of somatic mutations in the VH186.2 genes of the anti-NP IgG1/λ 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 VH 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.

Original languageEnglish
Pages (from-to)1161-1171
Number of pages11
JournalInternational Immunology
Volume16
Issue number8
DOIs
Publication statusPublished - Aug 1 2004
Externally publishedYes

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Antibody Formation
B-Lymphocytes
Immunoglobulin G
B-Cell Antigen Receptors
T-Lymphocytes
Anti-Idiotypic Antibodies
Chickens
Clone Cells
Antibody Affinity
Antibodies
Haptens
Genes
Immunoglobulin M
Antigens
Mutation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

BASH-deficient mice : Limited primary repertoire and antibody formation, but sufficient affinity maturation and memory B cell generation, in anti-NP response. / Yamamoto, Mutsumi; Nojima, Takuya; Hayashi, Katsuhiko; Goitsuka, Ryo; Furukawa, Koji; Azuma, Takachika; Kitamura, Daisuke.

In: International Immunology, Vol. 16, No. 8, 01.08.2004, p. 1161-1171.

Research output: Contribution to journalArticle

Yamamoto, Mutsumi ; Nojima, Takuya ; Hayashi, Katsuhiko ; Goitsuka, Ryo ; Furukawa, Koji ; Azuma, Takachika ; Kitamura, Daisuke. / BASH-deficient mice : Limited primary repertoire and antibody formation, but sufficient affinity maturation and memory B cell generation, in anti-NP response. In: International Immunology. 2004 ; Vol. 16, No. 8. pp. 1161-1171.
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