Engagement of CD40 lowers the threshold for activation of resting B cells via antigen receptor.
Cross-linking of surface Ig (sIg) on resting B cells can generate intracellular signals; however, for T-dependent antigens to promote growth and differentiation additional surface receptors must be engaged. Ligation of CD40 can stimulate B cell proliferation in the presence of interleukin-4. A recently identified counterstructure for CD40 is found on T helper cells and is believed to represent the cognate ligand for B cell activation. This study investigates the role of CD40 as an accessory molecule in sIg-dependent B cell activation. Simultaneous ligation of sIg and CD40 by monoclonal antibodies (mAb) in the presence of mouse L cells which express human Fc gamma receptor type II (Fc gamma RII-L cells) results in potent stimulation of small resting B cells. When CD40 is co-ligated, picomolar concentrations of mouse IgG1 anti-mu, and anti-delta mAb can stimulate B cell proliferation. This requires interaction of the anti-Ig mAb with the Fc gamma RII-L cells: a mouse IgG2a anti-mu mAb which is not recognized by Fc gamma RII, was > or = 1000-fold less effective. These findings suggest a mechanism for B cell activation whereby engagement of T cells via CD40 and its cognate ligand provides potent enhancement of signals delivered through sIg. Based on these observations, models for the activation of B cells by T-dependent antigens are presented.
Wheeler
K
K
Department of Immunology, Medical School, Birmingham, GB.
Pound
J D
JD
Gordon
J
J
Jefferis
R
R
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D011946:Receptors, Antigen / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D017452:Receptors, IgG / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D011946:Receptors, Antigen; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D015847:Interleukin-4