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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CCR10 is expressed on mucosal tissue lymphocytes with a PC phenotype. Ly...
CCR10 is expressed on mucosal tissue lymphocytes with a PC phenotype. Lymphocytes isolated from the gastrointestinal tract or tonsil were stained for CD19, CD20, and CD38 to define various B cell subsets (gated on large lymphocytes by scatter). (a) Both the colon and tonsil contained significant populations of both GC (CD38+CD19+CD20hi) and PC (CD38hiCD19+/–CD20–) phenotype B cells. GC cells did not express either CCR10 or CCR9 (<3% of GC cells in all tissues examined), while a fraction of PCs in the tonsil (22% ± 4%) and virtually all PCs in the colon (92% ± 4%) expressed CCR10. (b) CCR10 was also expressed on the vast majority of PCs in the jejunum (90% ± 7%), ileum (92% ± 5%), and stomach (87% ± 10%), and a significant fraction of cells in the appendix (38% ± 11%). CCR9 was present on PCs in the jejunum (36% ± 14%) and ileum (41% ± 18%) where TECK is also expressed and on PCs in the stomach (13% ± 7%). (c) GC cells in both the tonsil and colon expressed high levels of CD19 (>95% positive), while the phenotypically defined PC in both tissues had largely downregulated CD19 (<15% positive). Flow-cytometry data are representative of two tonsil, three stomach, three jejunum, three ileum, three colon, and two appendix samples with mean ± SD shown. Percentage of CCR10- or CCR9-positive cells based on quadrant encompassing 5% of isotype control-stained cells in dot blots.