The small rho GTPases Rac1 and Rac2 are important for T-cell independent antigen responses and for suppressing switching to IgG2b in Mice

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

B cells

Rac1

Rac2

Ig class switching

humoral immune response

mature b-cells

lymphocytes

cdc42

activation

adhesion

mutation

immunodeficiency

recombination

survival

protein

Immunology

B cells

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