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The role of RasGRPs in regulation of lymphocyte proliferation☆
- Source :
- Immunology Letters. 105:77-82
- Publication Year :
- 2006
- Publisher :
- Elsevier BV, 2006.
-
Abstract
- RasGRP1 links TCR signaling to Ras in T cells, while both RasGRP1 and RasGRP3 link BCR signaling to Ras in B cells. T cells deficient in RasGRP1 have defective proliferative responses as do B cells deficient in both RasGRP1 and RasGRP3, confirming the importance of Ras activation in lymphocyte proliferation. While aged Rasgrp1 −/− mice develop late-onset autoimmunity characterized by splenomegaly and the presence of anti-nuclear antibodies (ANA), the additional loss of RasGRP3 expression inhibits this phenotype. We show here that the autoimmunity in Rasgrp1 −/− mice is T cell dependent. Compared to wildtype, Rasgrp1 −/− T cells induce greater in vitro B cell proliferation that is due, at least in part, to increased production of interleukin-4 (IL-4). Rasgrp1 Rasgrp3 double mutant B cells are less responsive to this T cell stimulation. The reduced double mutant B cell proliferative response was paralleled by decreased induction of cyclin D2 upon stimulation with IL-4 and anti-IgM. Taken together these results suggest that double mutant mice fail to generate autoimmunity due to their decreased B cell cyclin D2 accumulation, and thus proliferation, in response to the elevated levels of IL-4 produced by mutant T cells.
- Subjects :
- CD4-Positive T-Lymphocytes
T cell
Immunology
Naive B cell
Receptors, Antigen, T-Cell
Mice, Nude
Receptors, Antigen, B-Cell
Autoimmunity
Lymphocyte proliferation
In Vitro Techniques
Biology
Lymphocyte Activation
Mice
Interleukin 21
medicine
Animals
Guanine Nucleotide Exchange Factors
Immunology and Allergy
Cytotoxic T cell
Lymphocytes
Antigen-presenting cell
B cell
Cell Proliferation
Mice, Knockout
B-Lymphocytes
ZAP70
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
Interleukin-4
Signal Transduction
Subjects
Details
- ISSN :
- 01652478
- Volume :
- 105
- Database :
- OpenAIRE
- Journal :
- Immunology Letters
- Accession number :
- edsair.doi.dedup.....618ff7e5fafe386a31a198eabe9510b9