IgA class switch in I alpha exon-deficient mice. Role of germline transcription in class switch recombination. (original) (raw)

Research Article Free access | 10.1172/JCI118438

Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.

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Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.

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Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.

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Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.

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Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.

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Published January 15, 1996 -More info

Published January 15, 1996 -Version history

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Abstract

Studies have implicated defective Ig class switch in the pathogenesis of IgA deficiency. To understand better the molecular events that regulate IgA class switch, a 1.4-kb region of the IgA locus containing the I alpha exon was replaced with a human hypoxanthine phosphoribosyltransferase minigene by gene targeting in murine embryonic stem cells. The I alpha exon-deficient mice derived from these embryonic stem cells had normal IgA levels in serum and secretions and normal numbers of IgA B cells in Peyer's patches and spleen. Further, I alpha exon-deficient B cells efficiently underwent IgA class switch in vitro, despite the absence of I alpha exon-containing germline transcripts. Notably, I alpha exon-deficient B cells did not require TGF-beta for IgA class switch since stimulation with LPS alone led to IgA expression. Nonetheless, whereas I alpha exon-deficient B cells constitutively expressed human hypoxanthine phosphoribosyltransferase transcripts, they did not produce IgA in the absence of LPS stimulation. These results demonstrate that the I alpha exon or transcripts containing the I alpha exon are not required for IgA class switch. Further, the effects of TGF-beta on I alpha locus transcription can be supplanted by expression of a heterologous minigene at that locus, but a second signal is required for the induction of IgA class switch.

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