| First Author | Harriman GR | Year | 1996 |
| Journal | J Clin Invest | Volume | 97 |
| Issue | 2 | Pages | 477-85 |
| PubMed ID | 8567970 | Mgi Jnum | J:72521 |
| Mgi Id | MGI:2153196 | Doi | 10.1172/JCI118438 |
| Citation | Harriman GR, et al. (1996) IgA class switch in I alpha exon-deficient mice. Role of germline transcription in class switch recombination. J Clin Invest 97(2):477-85 |
| abstractText | 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. |
