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The Journal of Immunology, 2004, 172: 2360-2366.
Copyright © 2004 by The American Association of Immunologists

Biases in Ig {lambda} Light Chain Rearrangements in Human Intestinal Plasma Cells 1

Wen Su*, Laurent Boursier*, Archana Padala*, Jeremy D. Sanderson{dagger} and Jo Spencer2,*

* Department of Histopathology, GKT Medical School, St. Thomas’ Campus, London, United Kingdom; and {dagger} Department of Gastroenterology, St. Thomas’ Hospital, London, United Kingdom

Human intestinal lamina propria plasma cells are considered to be the progeny of chronically stimulated germinal centers located in organized gut-associated lymphoid tissues such as Peyer’s patches and isolated lymphoid follicles. We have sampled human colonic lamina propria plasma cells and naive and memory B cell subsets from human Peyer’s patches by microdissection of immunohistochemically stained tissue sections and used PCR methods and sequence analysis to compare IgV{lambda}J{lambda} rearrangements in the plasma cell and B cell populations. Rearrangements that were either in-frame or out-of-frame between V and J were compared. Usage of IgV{lambda} families in the in-frame rearrangements from the plasma cells resembled that observed in the mantle cells, suggesting that antigenic selection for cellular specificity does not dramatically favor any particular V{lambda} segment. However, in marked contrast, out-of-frame rearrangements involving V{lambda}1 and V{lambda}2 families are rarely observed in intestinal plasma cells, whereas rearrangements involving V{lambda}5 are increased. This resulted in significantly biased ratios of in-frame:out-of-frame rearrangements in these V{lambda} families. Out-of-frame rearrangements of IgV{lambda}J{lambda} from plasma cells, including those involving the V{lambda}5 family, have a significant tendency not to involve J{lambda}1, consistent with the hypothesis that this population includes rearrangements generated by secondary recombination events. We propose that modification of out-of-frame rearrangements of IgV{lambda}J{lambda} exists, probably a consequence of secondary rearrangements. This may be a mechanism to avoid translocations to susceptible out-of-frame IgV{lambda}J{lambda} rearrangements during somatic hypermutation.




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W. Su, J. N. Gordon, F. Barone, L. Boursier, W. Turnbull, S. Mendis, D. K. Dunn-Walters, and J. Spencer
Lambda Light Chain Revision in the Human Intestinal IgA Response
J. Immunol., July 15, 2008; 181(2): 1264 - 1271.
[Abstract] [Full Text] [PDF]




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