CCR10 expression is a common feature of circulating and mucosal epithelial tissue IgA Ab-secreting cells
Eric J. Kunkel, Chang H. Kim, Nicole H. Lazarus, Mark A. Vierra, Dulce Soler, Edward P. Bowman, Eugene C. Butcher
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 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.