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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2009-03-01
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doaj-2d710e37a74e4f89a83faca68b52c3412021-04-21T17:23:57ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742009-03-0153e100033810.1371/journal.ppat.1000338The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity.Annemiek B van SprielMariam SofiKate H GartlanAlie van der SchaafIneke VerschuerenRuurd TorensmaReinier A P RaymakersBruce E LovelandMihai G NeteaGosse J AdemaMark D WrightCarl G FigdorImmunoglobulin 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19282981/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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. PLoS Pathogens |
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) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2009-03-01 |
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. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19282981/?tool=EBI |
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