The B cell SH2/PH domain-containing adaptor Bam32/DAPP1 is required for T cell-independent II antigen responses. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Bam32/DAPP1 is a B cell adaptor composed of both a PH and an SH2 domain. Previous studies in cell culture and chicken DT40 cells have indicated that Bam32 is critical for normal signaling downstream of the B cell receptor (BCR). RESULTS: We now study the function of Bam32 in mice in which Bam32 has been disrupted by a viral gene trap approach. Although B and T cell development is normal in Bam32(-/-) mice, B cell proliferation is reduced by about 50% after BCR crosslinking when compared with Bam32(+/+) mice. Differences in the activation of Erk, Jnk and p38 Map kinases, PLCgamma, and Ca(2+) flux do not account for the defect in proliferation as activation was similar in Bam32(+/+) and Bam32(-/-) B cells. Interestingly, whereas antibody response to T-dependent (TD) and T-independent (TI)-I antigens was similar between Bam32(+/+) and Bam32(-/-) mice, TI-II responses were defective in Bam32(-/-) mice; Bam32(-/-) mice failed to undergo isotype class switch recombination (CSR) to produce IgG3 antibodies due to a cell-autonomous defect in generation of IgG3 germline transcripts. The defect in TI-II antigen response led to an impaired antibody response to immunization with type 3 Streptococcus pneumoniae capsular polyschaccharide (PS), resulting in a markedly increased susceptibility to infection by Streptococcus pneumoniae. CONCLUSIONS: These findings indicate that Bam32 specifically couples an upstream signal to the IgG3 isotype heavy chain CSR and suggest that defects in Bam32 may account for the increased susceptibility to encapusulated organisms in a subset of immunodeficient patients.

publication date

  • October 28, 2003

Research

keywords

  • Adaptor Proteins, Signal Transducing
  • Antigens, T-Independent
  • B-Lymphocytes
  • Carrier Proteins
  • Lipoproteins
  • Membrane Proteins
  • Signal Transduction
  • src Homology Domains

Identity

Scopus Document Identifier

  • 0242286597

PubMed ID

  • 14588241

Additional Document Info

volume

  • 13

issue

  • 21