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Microbe-dependent CD11b+ IgA+ plasma cells mediate robust early-phase intestinal IgA responses in mice.

Kunisawa J, Gohda M, Hashimoto E, Ishikawa I, Higuchi M, Suzuki Y, Goto Y, Panea C, Ivanov II, Sumiya R, Aayam L, Wake T, Tajiri S, Kurashima Y, Shikata S, Akira S, Takeda K, Kiyono H - Nat Commun (2013)

Bottom Line: CD11b(+) IgA(+) plasma cells require the lymphoid structure of Peyer's patches, produce more IgA than CD11b(-) IgA(+) plasma cells, proliferate vigorously, and require microbial stimulation and IL-10 for their development and maintenance.These features allow CD11b(+) IgA(+) plasma cells to mediate early-phase antigen-specific intestinal IgA responses induced by oral immunization with protein antigen.These findings reveal the functional diversity of IgA(+) plasma cells in the murine intestine.

View Article: PubMed Central - PubMed

Affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. kunisawa@nibio.go.jp

ABSTRACT
Intestinal plasma cells predominantly produce immunoglobulin (Ig) A, however, their functional diversity remains poorly characterized. Here we show that murine intestinal IgA plasma cells can be newly classified into two populations on the basis of CD11b expression, which cannot be discriminated by currently known criteria such as general plasma cell markers, B cell origin and T cell dependence. CD11b(+) IgA(+) plasma cells require the lymphoid structure of Peyer's patches, produce more IgA than CD11b(-) IgA(+) plasma cells, proliferate vigorously, and require microbial stimulation and IL-10 for their development and maintenance. These features allow CD11b(+) IgA(+) plasma cells to mediate early-phase antigen-specific intestinal IgA responses induced by oral immunization with protein antigen. These findings reveal the functional diversity of IgA(+) plasma cells in the murine intestine.

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Role of IL-10 in the maintenance of CD11b+ IgA+ cells in the iLP.(a) Mice were treated with antibodies to block IL-5, IL-6, IL-10 or antagonistic TACI-immunoglobulin (TACI-Ig) fusion protein. Mononuclear cells were isolated from the iLP and used for analysis of CD11b+ and CD11b− IgA+ cells by flow cytometry. Data are presented as means±s.d. (n=4). (b) Mononuclear cells were isolated from the iLP of WT or IL-10 KO mice for analysis of IgA and CD11b expression by flow cytometry. Graphs show data from individual mice. Statistical analyses were performed with Mann–Whitney’s U-test.
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f5: Role of IL-10 in the maintenance of CD11b+ IgA+ cells in the iLP.(a) Mice were treated with antibodies to block IL-5, IL-6, IL-10 or antagonistic TACI-immunoglobulin (TACI-Ig) fusion protein. Mononuclear cells were isolated from the iLP and used for analysis of CD11b+ and CD11b− IgA+ cells by flow cytometry. Data are presented as means±s.d. (n=4). (b) Mononuclear cells were isolated from the iLP of WT or IL-10 KO mice for analysis of IgA and CD11b expression by flow cytometry. Graphs show data from individual mice. Statistical analyses were performed with Mann–Whitney’s U-test.

Mentions: We then examined the involvement of cytokines known to enhance IgA responses. Among several IgA-enhancing cytokines (for example, IL-5, IL-6, IL-10 and APRIL/BAFF)715, we found that neutralization of IL-10 resulted in preferential reduction in CD11b+ IgA+ PCs, whereas blocking of other cytokines induced a reduction in IgA+ cell numbers regardless of CD11b expression (Fig. 5a). Additionally, CD11b+ IgA+ cell numbers were preferentially reduced in IL-10 KO mice (Fig. 5b). As normal differentiation into IgA+ B cells was observed in the PPs and PerC of IL-10 KO mice (Supplementary Fig. S9), it is plausible that IL-10 targets the maintenance of CD11b+ IgA+ cells in the iLP, but not the induction of IgA+ cells in inductive tissues such as PPs and PerC.


Microbe-dependent CD11b+ IgA+ plasma cells mediate robust early-phase intestinal IgA responses in mice.

Kunisawa J, Gohda M, Hashimoto E, Ishikawa I, Higuchi M, Suzuki Y, Goto Y, Panea C, Ivanov II, Sumiya R, Aayam L, Wake T, Tajiri S, Kurashima Y, Shikata S, Akira S, Takeda K, Kiyono H - Nat Commun (2013)

Role of IL-10 in the maintenance of CD11b+ IgA+ cells in the iLP.(a) Mice were treated with antibodies to block IL-5, IL-6, IL-10 or antagonistic TACI-immunoglobulin (TACI-Ig) fusion protein. Mononuclear cells were isolated from the iLP and used for analysis of CD11b+ and CD11b− IgA+ cells by flow cytometry. Data are presented as means±s.d. (n=4). (b) Mononuclear cells were isolated from the iLP of WT or IL-10 KO mice for analysis of IgA and CD11b expression by flow cytometry. Graphs show data from individual mice. Statistical analyses were performed with Mann–Whitney’s U-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3644083&req=5

f5: Role of IL-10 in the maintenance of CD11b+ IgA+ cells in the iLP.(a) Mice were treated with antibodies to block IL-5, IL-6, IL-10 or antagonistic TACI-immunoglobulin (TACI-Ig) fusion protein. Mononuclear cells were isolated from the iLP and used for analysis of CD11b+ and CD11b− IgA+ cells by flow cytometry. Data are presented as means±s.d. (n=4). (b) Mononuclear cells were isolated from the iLP of WT or IL-10 KO mice for analysis of IgA and CD11b expression by flow cytometry. Graphs show data from individual mice. Statistical analyses were performed with Mann–Whitney’s U-test.
Mentions: We then examined the involvement of cytokines known to enhance IgA responses. Among several IgA-enhancing cytokines (for example, IL-5, IL-6, IL-10 and APRIL/BAFF)715, we found that neutralization of IL-10 resulted in preferential reduction in CD11b+ IgA+ PCs, whereas blocking of other cytokines induced a reduction in IgA+ cell numbers regardless of CD11b expression (Fig. 5a). Additionally, CD11b+ IgA+ cell numbers were preferentially reduced in IL-10 KO mice (Fig. 5b). As normal differentiation into IgA+ B cells was observed in the PPs and PerC of IL-10 KO mice (Supplementary Fig. S9), it is plausible that IL-10 targets the maintenance of CD11b+ IgA+ cells in the iLP, but not the induction of IgA+ cells in inductive tissues such as PPs and PerC.

Bottom Line: CD11b(+) IgA(+) plasma cells require the lymphoid structure of Peyer's patches, produce more IgA than CD11b(-) IgA(+) plasma cells, proliferate vigorously, and require microbial stimulation and IL-10 for their development and maintenance.These features allow CD11b(+) IgA(+) plasma cells to mediate early-phase antigen-specific intestinal IgA responses induced by oral immunization with protein antigen.These findings reveal the functional diversity of IgA(+) plasma cells in the murine intestine.

View Article: PubMed Central - PubMed

Affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. kunisawa@nibio.go.jp

ABSTRACT
Intestinal plasma cells predominantly produce immunoglobulin (Ig) A, however, their functional diversity remains poorly characterized. Here we show that murine intestinal IgA plasma cells can be newly classified into two populations on the basis of CD11b expression, which cannot be discriminated by currently known criteria such as general plasma cell markers, B cell origin and T cell dependence. CD11b(+) IgA(+) plasma cells require the lymphoid structure of Peyer's patches, produce more IgA than CD11b(-) IgA(+) plasma cells, proliferate vigorously, and require microbial stimulation and IL-10 for their development and maintenance. These features allow CD11b(+) IgA(+) plasma cells to mediate early-phase antigen-specific intestinal IgA responses induced by oral immunization with protein antigen. These findings reveal the functional diversity of IgA(+) plasma cells in the murine intestine.

Show MeSH
Related in: MedlinePlus