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A two‐signal model for regulation of immunoglobulin isotype switching
Author(s) -
Purkerson Jeffrey,
Isakson Peter
Publication year - 1992
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.6.14.1385241
Subject(s) - isotype , immunoglobulin class switching , antibody , immunology , signal (programming language) , microbiology and biotechnology , biology , computer science , b cell , monoclonal antibody , programming language
A characteristic feature of the humoral immune response is a switch from IgM to other Ig iso‐types that typically occurs subsequent to a first exposure to antigen, intimately, isotype switching involves a DNA rearrangement that recombines a variable region gene, initially juxtaposed to the μ constant region gene (C μ ), with a constant region gene located downstream of C μ. Isotype switching is controlled by T lymphocyte‐derived cytokines, such as interleukin‐4 (IL‐4), γ‐interferon (γ‐IFN), and TGF β , which direct B lymphocytes to switch to specific Ig classes. For example, IL‐4, directs murine B cells to produce IgG 1 and IgE, and human B cells to produce IgE and IgG 4 . IL‐4 appears to direct switching to IgE and IgG 1 by inducing transcription of the ∊ and γ1 constant region genes before switch recombination. However, IL‐4 is not a sufficient stimulus for isotype switching, and additional signals are required to complete this process. This second signal can be provided by physical contact with activated T cells, which may involve, at least in part, ligation of the CD40 molecule. For murine B cells the second signal may also be provided by IL‐5. Isotype switching in B lymphocytes may provide a useful model for directed DNA recombination in higher eukaryotes.— Purkerson, J.; Isakson, P. A two‐signal model for regulation of immunoglobin isotype switching. FASEB J. 6: 3245‐3252; 1992.