Cytokine dependency of human B cell cycle progression elicited by ligands which coengage BCR and the CD21/CD19/CD81 costimulatory complex.
Coengagement of BCR and the C3dg binding CD21/CD19/CD81 costimulatory complex can profoundly reduce the BCR binding threshold for eliciting B cell S phase entry, provided cytokine is present. IL-4 is substantially better than IL-2, IL-13, and TNF-alpha at exhibiting synergy with BCR:CD21 coengaging ligand (anti-IgM:anti-CD21:dextran) in promoting B cell DNA synthesis. Synergy between IL-4 and anti-IgM:anti-CD21:dextran (a) is not explained by the viability-promoting function of IL-4, (b) occurs when the anti-CD21 moiety engages either C3dg binding or non-C3dg binding domains, (c) does not reflect reversal of FcgammaRII-mediated negative regulation, and (d) involves differing temporal requirements for BCR and IL-4R signal transduction during the activation process. The IL-4R signaling pathway appears to synergize directly with the BCR:CD21 signaling pathway(s) in promoting the progression of resting B cells past an early G1 checkpoint, as well as to promote independently the progression of activated B cells past a later G1 to S checkpoint.
Department of Rheumatology, Hospital for Joint Diseases, New York, New York 10003, USA.
P K
PK
Mongini
J K
JK
Inman
D015703:Antigens, CD / Q000502:physiology*; D018941:Antigens, CD19 / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D002453:Cell Cycle; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D017464:Receptors, Complement 3d / Q000502:physiology*; D015398:Signal Transduction; D060225:Tetraspanin 28
D015703:Antigens, CD; D018941:Antigens, CD19; C554798:CD81 protein, human; D016207:Cytokines; D007376:Interleukin-2; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D017464:Receptors, Complement 3d; D060225:Tetraspanin 28; D015847:Interleukin-4; D007371:Interferon-gamma