ABSTRACT
The Th cells that regulate peritoneal B-1 cell functions have not yet been well characterized. To address this question, we investigated peritoneal CD4(+) T cells, observed a high frequency of the conjugates of B-CD4(+) T cells in the peritoneal cavity, and identified a population of CD49d(high)CD4(+) T cells that constituted about half of all CD4(+) T cells in the peritoneal cavity, but were rarely found in other compartments. Peritoneal CD49d(high)CD4(+) T cells were CD44(high)CD62L(low); expressed integrin α4ß1 and CXCR3; and rapidly secreted IFN-γ, TNF-α, and IL-2, showing features of proinflammatory Th1 cells. Peritoneal CD49d(high)CD4(+) T cells developed spontaneously, were detected at the age of 12 d, and showed stem cell-like properties. Their development was observed in mice deficient for signaling lymphocytic activation molecule-associated protein, but not in athymic nude mice and mice lacking in expression of MHC class II on thymic epithelial cells. Peritoneal CD49d(high)CD4(+) T cells were more resistant to irradiation and more sensitive to NAD-induced cell death than CD49d(low)CD4(+) T cells. Notably, peritoneal CD49d(high)CD4(+) T cells also showed some characteristics of follicular Th cells, such as the expression of programmed cell death 1, ICOS, IL-21, and CXCR5. Moreover, peritoneal CD49d(high)CD4(+) T cells enhanced the secretion of IgM Abs by B-1a cells and IgG Abs by splenic B cells. These data suggest that peritoneal CD49d(high)CD4(+) T cells may be innate-like CD4(+) T cells, which develop early and have a dual capacity to support both humoral and cellular immunity.
Subject(s)
B-Lymphocytes/immunology , Immunologic Memory , Integrin alpha4/immunology , Integrin alpha4beta1/immunology , Th1 Cells/immunology , Animals , B-Lymphocytes/cytology , Gene Expression Regulation, Developmental , Humans , Hyaluronan Receptors/genetics , Hyaluronan Receptors/immunology , Immunity, Cellular , Immunity, Humoral , Immunity, Innate , Integrin alpha4/genetics , Integrin alpha4beta1/genetics , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-2/genetics , Interleukin-2/immunology , L-Selectin/genetics , L-Selectin/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Nude , Peritoneal Cavity/cytology , Receptors, CXCR3/genetics , Receptors, CXCR3/immunology , Signal Transduction , Th1 Cells/cytology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunologyABSTRACT
CD138, known as a marker of plasma cells, was reported to be expressed to an intermediate level in the murine bone marrow precursor B cells. Here an intermediate level of CD138 expression was also noted in a subpopulation of splenic follicular B cells, which were distinguishable from CD138(high) plasma cells, whereas the majority of transitional or marginal zone B cells did not express CD138. These CD138(int) B cells were IgM(low)IgD(high) mature B cells, located within follicular B cell zone, and expressed a lower level of CD21 than CD138(-) follicular B cells. During in vitro culture of splenic cells, the proportion of CD138(int) B cells increased, which was noticeably reversed by the addition of IL-4 to the culture. The experiments with sorted CD138(int) cells showed that IL-4-mediated regulation of the CD138 expression was B cell-intrinsic and independent of in vitro B cell death. Our results demonstrate that mouse CD138(int) B cells characterize a subpopulation of IgM(low)IgD(high) mature follicular B cells. The CD138 expression on follicular B cells may represent a reversible status, reflecting a dynamic state probably influenced by IL-4.
Subject(s)
B-Lymphocytes/immunology , Down-Regulation/immunology , Interleukin-4/immunology , Syndecan-1/immunology , Animals , Antigens, CD19/immunology , Antigens, CD19/metabolism , Antigens, CD1d/immunology , Antigens, CD1d/metabolism , B-Lymphocyte Subsets/immunology , B-Lymphocyte Subsets/metabolism , B-Lymphocytes/metabolism , CD5 Antigens/immunology , CD5 Antigens/metabolism , Cells, Cultured , Down-Regulation/drug effects , Flow Cytometry , Immunoglobulin D/immunology , Immunoglobulin D/metabolism , Immunoglobulin M/immunology , Immunoglobulin M/metabolism , Interleukin-4/pharmacology , Leukosialin/immunology , Leukosialin/metabolism , Mice , Mice, Inbred C57BL , Microscopy, Fluorescence , Plasma Cells/immunology , Plasma Cells/metabolism , Receptors, Complement 3d/immunology , Receptors, Complement 3d/metabolism , Spleen/cytology , Spleen/immunology , Spleen/metabolism , Syndecan-1/metabolismABSTRACT
B-1 cells, which constitute a predominant lymphocyte subset in serosal cavities and produce most of natural antibodies, are subdivided into the CD5(+) B-1a and CD5(-) B-1b cell subpopulations, but the differential roles of B-1a and B-1b cells are not well understood. We report that B-1a cells preferentially migrate out of the peritoneal cavity and upregulate the expression of CXCR4 with heightened sensitivity to CXCL12 and CXCL13 upon LPS treatment compared to B-1b and B-2 cells. Whereas B-1a cells were slightly more abundant than B-1b and B-2 cells in the homeostatic condition, the number of B-1a cells preferentially decreased 48 hr after LPS treatment. The decrease in the peritoneal B-1a cell number was accompanied with increased migration of B-1a cells toward CXCL-12 and CXCL-13 in in vitro transmigration assay using peritoneal B cells from LPS treated mice. The expression level of CXCR4, but not of CXCR5, was also more prominently increased in B-1a cells upon LPS stimulation. LPS-stimulated B-1a cells did not accumulate in omental milky spots in contrast to B-2 cells. These results suggest that B-1a cells actively migrate out of the peritoneal cavity through the regulation of the migratory responsiveness to chemokines and actively participate in systemic immune responses.
