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Light Chain Rearrangements in Human Intestinal Plasma Cells 1

* Department of Histopathology, GKT Medical School, St. Thomas Campus, London, United Kingdom; and
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 Peyers patches and isolated lymphoid follicles. We have sampled human colonic lamina propria plasma cells and naive and memory B cell subsets from human Peyers patches by microdissection of immunohistochemically stained tissue sections and used PCR methods and sequence analysis to compare IgV
J
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
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
segment. However, in marked contrast, out-of-frame rearrangements involving V
1 and V
2 families are rarely observed in intestinal plasma cells, whereas rearrangements involving V
5 are increased. This resulted in significantly biased ratios of in-frame:out-of-frame rearrangements in these V
families. Out-of-frame rearrangements of IgV
J
from plasma cells, including those involving the V
5 family, have a significant tendency not to involve J
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
J
exists, probably a consequence of secondary rearrangements. This may be a mechanism to avoid translocations to susceptible out-of-frame IgV
J
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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