CCR10 expression is a common feature of circulating and mucosal epithelial tissue IgA Ab-secreting cells
Eric J. Kunkel, … , Edward P. Bowman, Eugene C. Butcher
Eric J. Kunkel, … , Edward P. Bowman, Eugene C. Butcher
Published April 1, 2003
Citation Information: J Clin Invest. 2003;111(7):1001-1010. https://doi.org/10.1172/JCI17244.
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CCR10 expression is a common feature of circulating and mucosal epithelial tissue IgA Ab-secreting cells

Abstract

The dissemination of IgA-dependent immunity between mucosal sites has important implications for mucosal immunoprotection and vaccine development. Epithelial cells in diverse gastrointestinal and nonintestinal mucosal tissues express the chemokine MEC/CCL28. Here we demonstrate that CCR10, a receptor for MEC, is selectively expressed by IgA Ab-secreting cells (large s/cIgA+CD38hiCD19int/–CD20–), including circulating IgA+ plasmablasts and almost all IgA+ plasma cells in the salivary gland, small intestine, large intestine, appendix, and tonsils. Few T cells in any mucosal tissue examined express CCR10. Moreover, tonsil IgA plasmablasts migrate to MEC, consistent with the selectivity of CCR10 expression. In contrast, CCR9, whose ligand TECK/CCL25 is predominantly restricted to the small intestine and thymus, is expressed by a fraction of IgA Ab-secreting cells and almost all T cells in the small intestine, but by only a small percentage of plasma cells and plasmablasts in other sites. These results point to a unifying role for CCR10 and its mucosal epithelial ligand MEC in the migration of circulating IgA plasmablasts and, together with other tissue-specific homing mechanisms, provides a mechanistic basis for the specific dissemination of IgA Ab-secreting cells after local immunization.

Authors

Eric J. Kunkel, Chang H. Kim, Nicole H. Lazarus, Mark A. Vierra, Dulce Soler, Edward P. Bowman, Eugene C. Butcher

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Figure 5

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Subsets of circulating blood IgA plasmablasts express CCR10 and CCR9. Pe...
Subsets of circulating blood IgA plasmablasts express CCR10 and CCR9. Peripheral blood lymphocytes were isolated, depleted of T cells, and stained for surface IgA (sIgA) or surface IgG (sIgG), CD19, a dump cocktail (CD14, CD3, IgD, and CD94), and CCR10, CCR9, or CCR6. (a) Of small memory lymphocytes expressing sIgA (CD19+sIgA+; 4% ± 2% of total CD19+ cells), few expressed CCR10 (3% ± 2%), while a small population expressed CCR9 (16% ± 5%), and virtually all expressed CCR6 (98% ± 1%). (b) Two discernable populations of dump cocktail–negative lymphocytes in the large lymphocyte gate could be identified by expression of sIgA and CD19. Large lymphocytes with an IgA memory phenotype (sIgA+CD19+) expressed CCR10 (4% ± 1%), CCR9 (28% ± 3%), and CCR6 (90% ± 2%) in a pattern similar to small sIgA+ memory lymphocytes. A large fraction of lymphocytes with an IgA plasmablast phenotype (sIgAintCD19int; roughly 0.1% of total CD19+ cells) expressed CCR10 (72% ± 8%), and a smaller fraction expressed CCR9 (17% ± 13%), while few expressed CCR6 (13% ± 3%). (c) The majority (>90%) of sIgA-CD19+/int lymphocytes (shown in b by box) are sIgG+. IgG+ memory lymphocytes (sIgG+CD19+) did not express CCR10 (3% ± 2%), while some expressed CCR9 (14% ± 3%), and almost all expressed CCR6 (84% ± 6%). Plasmablasts expressing sIgG (sIgG+CD19int) contained some CCR10+ (13% ± 6%) and CCR9+ (16% ± 7%) lymphocytes and few CCR6+ (18% ± 4%) cells. Data are representative of four experiments from separate blood donors with data averaged across donors (mean ± SD).