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SHR Neuro Cancer Cardio Lipid Metab Microb
Burbage, M; Keppler, SJ; Montaner, B; Mattila, PK; Batista, FD.
The Small Rho GTPase TC10 Modulates B Cell Immune Responses.
J Immunol. 2017; 199(5): 1682-1695.
Doi: 10.4049/jimmunol.1602167
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- Co-authors Med Uni Graz
- Keppler Selina Jessica
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- Abstract:
- Rho family GTPases regulate diverse cellular events, such as cell motility, polarity, and vesicle traffic. Although a wealth of data exists on the canonical Rho GTPases RhoA, Rac1, and Cdc42, several other family members remain poorly studied. In B cells, we recently demonstrated a critical role for Cdc42 in plasma cell differentiation. In this study, we focus on a close homolog of Cdc42, TC10 (also known as RhoQ), and investigate its physiological role in B cells. By generating a TC10-deficient mouse model, we show that despite reduced total B cell numbers, B cell development in these mice occurs normally through distinct developmental stages. Upon immunization, IgM levels were reduced and, upon viral infection, germinal center responses were defective in TC10-deficient mice. BCR signaling was mildly affected, whereas cell migration remained normal in TC10-deficient B cells. Furthermore, by generating a TC10/Cdc42 double knockout mouse model, we found that TC10 can compensate for the lack of Cdc42 in TLR-induced cell activation and proliferation, so the two proteins play partly redundant roles. Taken together, by combining in vivo and in vitro analysis using TC10-deficient mice, we define the poorly studied Rho GTPase TC10 as an immunomodulatory molecule playing a role in physiological B cell responses.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- B-Lymphocytes - immunology
- Cell Differentiation - administration & dosage
- Cell Proliferation - administration & dosage
- Cells, Cultured - administration & dosage
- Germinal Center - immunology
- Immunomodulation - administration & dosage
- Lymphocyte Activation - administration & dosage
- Mice - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- Mice, Knockout - administration & dosage
- Orthomyxoviridae Infections - immunology
- Receptors, Antigen, B-Cell - metabolism
- Signal Transduction - administration & dosage
- Vaccinia - immunology
- cdc42 GTP-Binding Protein - genetics, metabolism
- rho GTP-Binding Proteins - genetics, metabolism