Elsevier

Molecular Immunology

Volume 33, Issues 17–18, December 1996, Pages 1335-1343
Molecular Immunology

Direct evidence that γ1 and γ3 switching in human B cells is interleukin-10 dependent

https://doi.org/10.1016/S0161-5890(96)00092-2Get rights and content

Abstract

Interleukin-10 (IL-10) has various effects on B cell immunoglobulin (Ig) production. Indirect evidence suggests that IL-10 functions as a switch factor for IgG production. In this study, the switch deleted Ig gene DNA was isolated and characterized, as direct evidence that IL-10 induced isotype switching in human B cells. In addition, 16 chimeric Ig fragments were isolated, representing deleted DNA generated by in vitro isotype switching from μ to γ in human B cells, following stimulation with IL-10 and anti-CD40 monoclonal antibodies (CD40 mAb). These clones consisted solely of Sγ1 and Sγ3 chimeric switch circular DNAs, no Sγ2 or Sγ4 switch DNA was observed. In addition, IL-10 alone induced only γ1 and γ3 germ-line mRNA transcripts, as determined by restriction digestion of the reverse transcription-polymerase chain reaction products. Three modes of μ-γ3 isotype switching were detected: (1) direct switching; (2) internal deletion of Sμ proceeding μ to γ3 switching; and (3) internal deletion of Sγ3 proceeding μ to γ3 switching. These results directly demonstrate that γ1 and γ3 switching in human B cells is specifically induced by IL-10 in the presence of CD40 mAb.

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