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Lambda Light Chain Revision in the Human Intestinal IgA Response¹

Wen Su^*, John N. Gordon, Francesca Barone^*, Laurent Boursier^*, Wayne Turnbull^*, Surangi Mendis^*, Deborah K. Dunn-Walters^* and Jo Spencer^2,*

^* Department of Immunobiology, Kings College London School of Medicine at Guy’s King’s College and St. Thomas’ Hospitals, London, United Kingdom; and Division of Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom

Revision of Ab L chains by secondary rearrangement in mature B cells has the potential to change the specific target of the immune response. In this study, we show for the first time that L chain revision is normal and widespread in the largest Ab producing population in man: intestinal IgA plasma cells (PC). Biases in the productive and non-productive repertoire of L chains, identification of the circular products of rearrangement that have the characteristic biases of revision, and identification of RAG genes and protein all reflect revision during normal intestinal IgA PC development. We saw no evidence of IgH revision, probably due to inappropriately orientated recombination signal sequences, and little evidence of -chain revision, probably due to locus inactivation by the -deleting element. We propose that the L chain locus is available and a principal modifier and diversifier of Ab specificity in intestinal IgA PCs.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council.

² Address correspondence and reprint requests to Dr. Jo Spencer, Department of Immunobiology, Kings College London School of Medicine at Guy’s King’s College and St. Thomas’ Hospitals, Guy’s Campus, St. Thomas’ Street, London SE1 9RT, U.K. E-mail address: jo.spencer{at}kcl.ac.uk

³ Abbreviations used in this paper: PC, plasma cell; , L chain; , L chain; KDE, kappa-deleting element; REC, recombination excision circle; RSS, recombination signal sequence; AID, activation-induced deaminase.