ROLES OF NASAL B-1 AND B-2 CELLS IN PROTECTIVE IMMUNITY
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B cells can be separated into at least two subsets, B-1 and B-2 cells, based on the expression of CD5 and CD45R/B220. B-1 cells are phenotypically and functionally distinct from conventional B cells (B-2 cells). B-1 cells predominate in the peritoneal and pleural cavities and in the lamina propria of the gut and play important roles in protective immunity as a major source of mucosal IgA. Although intestinal B-1 cells are well documented, the nature of B-1 cells in the upper respiratory tract remains unknown. In this study, we analyzed the characteristics of nasal B-1 cells at the single cell level. Mononuclear cells (MNCs) were isolated from the nasal passage (NP), nasal-associated lymphoid tissue (NALT), cervical lymph node (CLN), and spleen (SP) of normal mice. The frequency of B-1 and B-2 cells was analyzed by flow cytometry. B-1 and B-2 cells from the NP were purified, and isotype-specific antibody-producing cells were determined by enzyme-linked immunospot (ELISPOT) assay. To investigate antigen-specific immune responses in B-1 and B-2 cells, MNCs were isolated from the NP of orally cholera toxin (CT)-immunized mice and alterations after antigen exposure were analyzed using flow cytometry and a CT-specific ELISPOT assay. B-1 cells were predominant in the B cells found in the NP but accounted for only a few percent in the SP and were rare in NALT and the CLN. In addition, B-1 cells were the major producers of IgA in the NP. Interestingly, B-2 cells increased in the NP after immunization, and these B-2 cells produced larger amounts of CT-specific IgA than the B-1 cells. These results suggest that B-1 cells constitute a primitive immune system and play a role in the protective immunity that forms a first line of defense. Furthermore, B-2 cells can contribute to mucosal IgA responses via the common mucosal immune system. These findings suggest that two distinct lineages of IgA B cells developing from B-1 and B-2 cells are involved in the formation of the mucosal barrier in the upper respiratory tract.NP: nasal passage NALT: nasal-associated lymphoid tissue CLN: cervical lymph node SP: spleen CMIS: common mucosal immune system CT: cholera toxin
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