The Rac2 guanosine triphosphatase regulates B lymphocyte antigen receptor responses and chemotaxis and is required for establishment of B-1a and marginal zone B lymphocytes.
We have defined roles for the hemopoietic-specific Rho guanosine triphosphatase, Rac2, in B lymphocyte development and function through examination of rac2(-/-) mice. Rac2-deficient mice displayed peripheral blood B lymphocytosis and marked reductions in peritoneal cavity B-1a lymphocytes, marginal zone B lymphocytes, and IgM-secreting plasma cells as well as reduced concentrations of serum IgM and IgA. The rac2(-/-) B lymphocytes exhibited reduced calcium flux following coligation of B cell AgR and CD19 and reduced chemotaxis in chemokine gradients. T cell-independent responses to DNP-dextran were of reduced magnitude, but normal kinetics, in rac2(-/-) mice, while T-dependent responses to nitrophenyl-keyhole limpet hemocyanin were subtly abnormal. Rac2 is therefore an essential element in regulating B lymphocyte functions and maintaining B lymphocyte populations in vivo.
Croker
Ben A
BA
Division of Cancer and Hematology and Immunology, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Tarlinton
David M
DM
Cluse
Leonie A
LA
Tuxen
Alana J
AJ
Light
Amanda
A
Yang
Feng-Chun
FC
Williams
David A
DA
Roberts
Andrew W
AW
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000921:Antibody-Producing Cells / Q000473:pathology; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D000955:Antigens, T-Independent / Q000494:pharmacology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002464:Cell Migration Inhibition; D018925:Chemokines / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D006241:Haptens; D006433:Hemocyanins / Q000494:pharmacology; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D020744:rac GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000097766:RAC2 GTP-Binding Protein
D000199:Actins; D018941:Antigens, CD19; D000955:Antigens, T-Independent; D002118:Calcium; D018925:Chemokines; D006241:Haptens; D006433:Hemocyanins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C098951:4-hydroxy-3-nitrophenylacetyl-keyhole limpet hemocyanin