Complement-Activating IgM Enhances the Humoral but Not the T Cell Immune Response in Mice

IgM antibodies specific for a certain antigen can enhance antibody responses when administered together with this antigen, a process believed to require complement activation by IgM. However, recent data show that a knock-in mouse strain, Cμ13, which only produces IgM unable to activate complement,...

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Main Authors:	Ding, Zhoujie, Bergman, Anna, Rutemark, Christian, Ouchida, Rika, Ohno, Hiroshi, Wang, Ji-Yang, Heyman, Birgitta
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826713/

id	pubmed-3826713
recordtype	oai_dc
spelling	pubmed-38267132013-11-18 Complement-Activating IgM Enhances the Humoral but Not the T Cell Immune Response in Mice Ding, Zhoujie Bergman, Anna Rutemark, Christian Ouchida, Rika Ohno, Hiroshi Wang, Ji-Yang Heyman, Birgitta Research Article IgM antibodies specific for a certain antigen can enhance antibody responses when administered together with this antigen, a process believed to require complement activation by IgM. However, recent data show that a knock-in mouse strain, Cμ13, which only produces IgM unable to activate complement, has normal antibody responses. Moreover, the recently discovered murine IgM Fc receptor (FcµR or TOSO/FAIM3) was shown to affect antibody responses. This prompted the re-investigation of whether complement activation by specific IgM is indeed required for enhancement of antibody responses and whether the mutation in Cµ13 IgM also caused impaired binding to FcµR. The results show that IgM from Cµ13 and wildtype mice bound equally well to the murine FcµR. In spite of this, specific Cμ13 IgM administered together with sheep red blood cells or keyhole limpet hemocyanine was a very poor enhancer of the antibody and germinal center responses as compared with wildtype IgM. Within seconds after immunization, wildtype IgM induced deposition of C3 on sheep red blood cells in the blood. IgM which efficiently enhanced the T-dependent humoral immune response had no effect on activation of specific CD4+ T cells as measured by cell numbers, cell division, blast transformation, or expression of the activation markers LFA-1 and CD44 in vivo. These observations confirm the importance of complement for the ability of specific IgM to enhance antibody responses and suggest that there is a divergence between the regulation of T- and B-cell responses by IgM. Public Library of Science 2013-11-08 /pmc/articles/PMC3826713/ /pubmed/24250831 http://dx.doi.org/10.1371/journal.pone.0081299 Text en © 2013 Ding et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ding, Zhoujie Bergman, Anna Rutemark, Christian Ouchida, Rika Ohno, Hiroshi Wang, Ji-Yang Heyman, Birgitta
spellingShingle	Ding, Zhoujie Bergman, Anna Rutemark, Christian Ouchida, Rika Ohno, Hiroshi Wang, Ji-Yang Heyman, Birgitta Complement-Activating IgM Enhances the Humoral but Not the T Cell Immune Response in Mice
author_facet	Ding, Zhoujie Bergman, Anna Rutemark, Christian Ouchida, Rika Ohno, Hiroshi Wang, Ji-Yang Heyman, Birgitta
author_sort	Ding, Zhoujie
title	Complement-Activating IgM Enhances the Humoral but Not the T Cell Immune Response in Mice
title_short	Complement-Activating IgM Enhances the Humoral but Not the T Cell Immune Response in Mice
title_full	Complement-Activating IgM Enhances the Humoral but Not the T Cell Immune Response in Mice
title_fullStr	Complement-Activating IgM Enhances the Humoral but Not the T Cell Immune Response in Mice
title_full_unstemmed	Complement-Activating IgM Enhances the Humoral but Not the T Cell Immune Response in Mice
title_sort	complement-activating igm enhances the humoral but not the t cell immune response in mice
description	IgM antibodies specific for a certain antigen can enhance antibody responses when administered together with this antigen, a process believed to require complement activation by IgM. However, recent data show that a knock-in mouse strain, Cμ13, which only produces IgM unable to activate complement, has normal antibody responses. Moreover, the recently discovered murine IgM Fc receptor (FcµR or TOSO/FAIM3) was shown to affect antibody responses. This prompted the re-investigation of whether complement activation by specific IgM is indeed required for enhancement of antibody responses and whether the mutation in Cµ13 IgM also caused impaired binding to FcµR. The results show that IgM from Cµ13 and wildtype mice bound equally well to the murine FcµR. In spite of this, specific Cμ13 IgM administered together with sheep red blood cells or keyhole limpet hemocyanine was a very poor enhancer of the antibody and germinal center responses as compared with wildtype IgM. Within seconds after immunization, wildtype IgM induced deposition of C3 on sheep red blood cells in the blood. IgM which efficiently enhanced the T-dependent humoral immune response had no effect on activation of specific CD4+ T cells as measured by cell numbers, cell division, blast transformation, or expression of the activation markers LFA-1 and CD44 in vivo. These observations confirm the importance of complement for the ability of specific IgM to enhance antibody responses and suggest that there is a divergence between the regulation of T- and B-cell responses by IgM.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826713/
_version_	1612026309842567168

Complement-Activating IgM Enhances the Humoral but Not the T Cell Immune Response in Mice

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