The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity.

Immunoglobulin A (IgA) secretion by plasma cells in the immune system is critical for protecting the host from environmental and microbial infections. However, the molecular mechanisms underlying the generation of IgA(+) plasma cells remain poorly understood. Here, we report that the B cell-expresse...

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Autores principales:	Annemiek B van Spriel, Mariam Sofi, Kate H Gartlan, Alie van der Schaaf, Ineke Verschueren, Ruurd Torensma, Reinier A P Raymakers, Bruce E Loveland, Mihai G Netea, Gosse J Adema, Mark D Wright, Carl G Figdor
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2d710e37a74e4f89a83faca68b52c341
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spelling	oai:doaj.org-article:2d710e37a74e4f89a83faca68b52c3412021-11-25T05:47:12ZThe tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity.1553-73661553-737410.1371/journal.ppat.1000338https://doaj.org/article/2d710e37a74e4f89a83faca68b52c3412009-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19282981/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Immunoglobulin A (IgA) secretion by plasma cells in the immune system is critical for protecting the host from environmental and microbial infections. However, the molecular mechanisms underlying the generation of IgA(+) plasma cells remain poorly understood. Here, we report that the B cell-expressed tetraspanin CD37 inhibits IgA immune responses in vivo. CD37-deficient (CD37-/-) mice exhibit a 15-fold increased level of IgA in serum and significantly elevated numbers of IgA(+) plasma cells in spleen, mucosal-associated lymphoid tissue, as well as bone marrow. Analyses of bone marrow chimeric mice revealed that CD37-deficiency on B cells was directly responsible for the increased IgA production. We identified high local interleukin-6 (IL-6) production in germinal centers of CD37-/- mice after immunization. Notably, neutralizing IL-6 in vivo reversed the increased IgA response in CD37-/- mice. To demonstrate the importance of CD37-which can associate with the pattern-recognition receptor dectin-1-in immunity to infection, CD37-/- mice were exposed to Candida albicans. We report that CD37-/- mice are evidently better protected from infection than wild-type (WT) mice, which was accompanied by increased IL-6 levels and C. albicans-specific IgA antibodies. Importantly, adoptive transfer of CD37-/- serum mediated protection in WT mice and the underlying mechanism involved direct neutralization of fungal cells by IgA. Taken together, tetraspanin protein CD37 inhibits IgA responses and regulates the anti-fungal immune response.Annemiek B van SprielMariam SofiKate H GartlanAlie van der SchaafIneke VerschuerenRuurd TorensmaReinier A P RaymakersBruce E LovelandMihai G NeteaGosse J AdemaMark D WrightCarl G FigdorPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 3, p e1000338 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Annemiek B van Spriel Mariam Sofi Kate H Gartlan Alie van der Schaaf Ineke Verschueren Ruurd Torensma Reinier A P Raymakers Bruce E Loveland Mihai G Netea Gosse J Adema Mark D Wright Carl G Figdor The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity.
description	Immunoglobulin A (IgA) secretion by plasma cells in the immune system is critical for protecting the host from environmental and microbial infections. However, the molecular mechanisms underlying the generation of IgA(+) plasma cells remain poorly understood. Here, we report that the B cell-expressed tetraspanin CD37 inhibits IgA immune responses in vivo. CD37-deficient (CD37-/-) mice exhibit a 15-fold increased level of IgA in serum and significantly elevated numbers of IgA(+) plasma cells in spleen, mucosal-associated lymphoid tissue, as well as bone marrow. Analyses of bone marrow chimeric mice revealed that CD37-deficiency on B cells was directly responsible for the increased IgA production. We identified high local interleukin-6 (IL-6) production in germinal centers of CD37-/- mice after immunization. Notably, neutralizing IL-6 in vivo reversed the increased IgA response in CD37-/- mice. To demonstrate the importance of CD37-which can associate with the pattern-recognition receptor dectin-1-in immunity to infection, CD37-/- mice were exposed to Candida albicans. We report that CD37-/- mice are evidently better protected from infection than wild-type (WT) mice, which was accompanied by increased IL-6 levels and C. albicans-specific IgA antibodies. Importantly, adoptive transfer of CD37-/- serum mediated protection in WT mice and the underlying mechanism involved direct neutralization of fungal cells by IgA. Taken together, tetraspanin protein CD37 inhibits IgA responses and regulates the anti-fungal immune response.
format	article
author	Annemiek B van Spriel Mariam Sofi Kate H Gartlan Alie van der Schaaf Ineke Verschueren Ruurd Torensma Reinier A P Raymakers Bruce E Loveland Mihai G Netea Gosse J Adema Mark D Wright Carl G Figdor
author_facet	Annemiek B van Spriel Mariam Sofi Kate H Gartlan Alie van der Schaaf Ineke Verschueren Ruurd Torensma Reinier A P Raymakers Bruce E Loveland Mihai G Netea Gosse J Adema Mark D Wright Carl G Figdor
author_sort	Annemiek B van Spriel
title	The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity.
title_short	The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity.
title_full	The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity.
title_fullStr	The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity.
title_full_unstemmed	The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity.
title_sort	tetraspanin protein cd37 regulates iga responses and anti-fungal immunity.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/2d710e37a74e4f89a83faca68b52c341
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The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity.

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