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Prepublished online as a Blood First Edition Paper on July 24, 2003; DOI 10.1182/blood-2003-03-0947. This Article Full Text (PDF) All Versions of this Article: 2003-03-0947v1 102/12/4076    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Underhill, G. H Articles by Kansas, G. S Search for Related Content PubMed PubMed Citation Articles by Underhill, G. H Articles by Kansas, G. S Social Bookmarking                   What's this? Submitted March 27, 2003 Accepted July 12, 2003 Complexity within the plasma cell compartment of mice deficient in both E- and P-selectin: implications for plasma cell differentiation Gregory H Underhill, K Pallav Kolli, and Geoffrey S Kansas* Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA Department of Microbiology-Immunology, Feinberg School of Medicine of Northwestern University, Chicago, IL, USA * Corresponding author; email: gsk{at}northwestern.edu. Antibody secreting plasma cells represent the critical end-stage effector cells of the humoral immune response. Here, we show that several distinct plasma cell subsets are concurrently present in the lymph nodes, spleen, and bone marrow of mice deficient in both E- and P-selectin. One of these subsets was a B220-negative IgG plasma cell population expressing low to negative surface levels of syndecan-1. Examination of the chemotactic responsiveness of IgG plasma cell subsets revealed that migration towards SDF-1/CXCL12 was primarily limited to the B220-lo subset regardless of tissue source. Although B220-negative plasma cells did not migrate efficiently in response to CXCL12 or to other chemokines for which receptor mRNA was expressed, these cells expressed substantial surface CXCR4, and CXCL12 stimulation rapidly induced ERK1/ERK2 phosphorylation, demonstrating that CXCR4 retained signaling capacity. Therefore, B220-negative plasma cells exhibit a selective uncoupling of chemokine receptor expression and signaling from migration. Taken together, our findings document the presence of significant heterogeneity within the plasma cell compartment, which suggests a complex step-wise scheme of plasma cell differentiation in which the degree of differentiation and tissue location can influence the chemotactic responsiveness of IgG plasma cells. 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