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The small rho GTPases Rac1 and Rac2 are important for T-cell independent antigen responses and for suppressing switching to IgG2b in Mice
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Gothenburg, Sweden.
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Number of Authors: 6
2017 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, 1264Article in journal (Refereed) Published
Abstract [en]

The Rho GTPases Cdc42, Rac1, and Rac2 coordinate receptor signaling to cell adhesion, migration, and proliferation. Deletion of Rac1 and Rac2 early during B cell development leads to failure in B cell entry into the splenic white pulp. Here, we sought to understand the role of Rac1 and Rac2 in B cell functionality and during the humoral antibody response. To circumvent the migratory deficiency of B cells lacking both Rac1 and Rac2, we took the approach to inducibly delete Rac1 in Rac2(-/-) B cells in the spleen (Rac1(B)Rac2(-/-) B cells). Rac1(B)Rac2(-/-) mice had normal differentiation of splenic B cell populations, except for a reduction in marginal zone B cells. Rac1(B)Rac2(-/-) B cells showed normal spreading response on antibody-coated layers, while both Rac2(-/-) and Rac1(B)Rac2(-/-) B cells had reduced homotypic adhesion and decreased proliferative response when compared to wild-type B cells. Upon challenge with the T-cell-independent antigen TNP-conjugated lipopolysaccharide, Rac1(B)Rac2(-/-) mice showed reduced antibody response. In contrast, in response to the T-cell-dependent antigen sheep red blood cells, Rac1(B)Rac2(-/-) mice had increased serum titers of IgG1 and IgG2b. During in vitro Ig class switching, Rac1(B)Rac2(-/-) B cells had elevated germline gamma 2b transcripts leading to increased Ig class switching to IgG2b. Our data suggest that Rac1 and Rac2 serve an important role in regulation of the B cell humoral immune response and in suppressing Ig class switching to IgG2b.

Place, publisher, year, edition, pages
2017. Vol. 8, 1264
Keyword [en]
B cells, Rac1, Rac2, Ig class switching, humoral immune response
National Category
Biological Sciences Immunology in the medical area
Identifiers
URN: urn:nbn:se:su:diva-148933DOI: 10.3389/fimmu.2017.01264ISI: 000412508200001PubMedID: 29056938OAI: oai:DiVA.org:su-148933DiVA: diva2:1156807
Available from: 2017-11-14 Created: 2017-11-14 Last updated: 2017-11-29Bibliographically approved

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