Surface, membrane-bound, immunoglobulin M (IgM) or IgD expression early in B cell ontogeny is considered essential for the differentiation of antibody-producing cells in mammals; only in IgM+ B cells is the heavy chain locus rearranged to express antibodies of other classes. We show here that IgA is selectively expressed in μMT mice, which lack IgM or IgD expression and have a pro-B cell developmental block. μMT IgA binds proteins of commensal intestinal bacteria and is weakly induced by Salmonella infection, although not through conventional immunization. This μMT IgA pathway requires extrasplenic peripheral lymphoid tissues and may be an evolutionarily primitive system in which immature B cells switch to IgA production at peripheral sites.
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We thank T. Uhr and the staff of the Labortierkunde, Universität Zürich, for technical assistance and E. Wagner of the Basel Institute and F. Ronchese of the Malaghan Institute of Medical Research for serum samples from their μMT colonies. Supported by the Swiss Nationalfonds (grant numbers 31-50900.97 and 31-50884.97), the Kanton of Zürich and the Medical Research Council of Canada (A. L.).
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The H2B deubiquitinase Usp22 promotes antibody class switch recombination by facilitating non-homologous end joining
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