Role of cytokines in human B lymphocyte growth and differentiation.
B lymphocytes express at their surface the CD40 antigen which belongs to the NGF receptor superfamily. The crosslinking of the CD40 antigen using a mouse fibroblastic cell line expressing the human Fc receptor (Fc gamma RII/CDw32) and anti-CD40 monoclonal antibody induces resting B lymphocytes to enter a state of sustained proliferation. Addition of IL-4 to such cultures results in the generation of factor dependent long-term normal human B cell lines and in the secretion of IgE following isotype switching. Addition of IL-10 results in limited cell proliferation but most importantly in very high immunoglobulin production which results from the differentiation of B cells into plasma cells. The combination of IL-10 and TGF beta induces naive sIgD+ sIgM+ B cells to secrete IgA1 and IgA2 as a consequence of isotype switching. The extracellular domain of CD40 binds with high affinity and high specificity to a 32 kDa glycoprotein transiently expressed on activated T cells. This interaction of the CD40 antigen on B cells with its ligand on T cells represents a key step in T cell dependent B cell activation.
Banchereau
J
J
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Blanchard
D
D
Brière
F
F
Galizzi
J P
JP
Garrone
P
P
Hermann
P
P
Lebecque
S
S
Rousset
F
F
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology*; D017252:CD3 Complex / Q000502:physiology; D019013:CD40 Antigens; D002454:Cell Differentiation; D002455:Cell Division; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D008211:Lymphocyte Cooperation; D008954:Models, Biological
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D017252:CD3 Complex; D019013:CD40 Antigens; D016207:Cytokines