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.
View: Text | PDF
Article Aging

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

×

Figure 4

Options: View larger image (or click on image) Download as PowerPoint
MEC is chemotactic for tonsil IgA plasmablasts expressing CCR10. (a) Ton...
MEC is chemotactic for tonsil IgA plasmablasts expressing CCR10. (a) Tonsil lymphocytes were migrated to medium, SDF-1α (100 nM), TECK (300 nM), or MEC (300 nM) and stained for sIgA, CD19, CD20, and CD38 to identify plasmablasts and plasma cells in the large lymphocyte gate. Only sIgA+ B cells with a plasmablast phenotype migrated well to MEC. Plasmablasts did not migrate well to TECK. (b) Consistent with their migration to MEC, tonsil plasmablasts and plasma cells (CD38hiCD20–) express CCR10 (60% ± 14% of sIgA+ plasmablasts and 21% ± 13% of sIgAlo/– PCs), while the lack of a TECK response is consistent with the small number of cells expressing CCR9 (10% ± 6% of sIgA+ plasmablasts and 4% ± 2% of sIgAlo/– PCs). Data are representative of two independent experiments with multiple wells per experiment (the percentage of cells expressing CCR10 or CCR9 is averaged over both experiments, mean ± SD). As stated, the percentages shown in b are the percentages of sIgA+ or sIgA– plasma cells expressing each receptor. Background migration was <1% in both cell populations.