Defective early T and T-dependent B cell activation in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is characterized by autoantibody production of unknown origin. Since T-B cell interaction is a key event to produce antibodies, we investigated this interaction through study of CD69, CD40 ligand (CD40L) and CD23 expression (three very early activation antigens). Peripheral blood mononuclear cells (PBMC) from inactive lupus patients were studied following culture with either medium alone, anti-CD3 monoclonal antibody (mAb), recombinant interleukin-4 (rIL-4) or phorbol myristate acetate (PMA)+/-ionomycin. Analysis of CD23 expression on lupus B cells in basal conditions and after anti-CD3 challenge of PBMC, a reflection of cognate interaction between T and B cells, was clearly defective. Conversely, CD23 expression on lupus B cells following non-cognate T cell signals (rIL-4) was preserved. CD69 and CD40L expression was also impaired in lupus T cells following anti-CD3 challenge. Nonetheless, activation by means of PMA and/or ionomycin was preserved both in T cells (CD69 and CD40L expression) and in B cells (CD23 expression). These results indicate that B cells from inactive lupus patients display a normal early response to direct B-cell stimuli. Conversely, T-dependent B-cell stimuli are clearly defective in SLE patients in remission. These results indicate that T-B cognate interaction related to defective T cell activation located between surface membrane and protein kinase C (PKC)/ionomycin function is an intrinsic characteristic of these patients.
Rheumatology Service, Hospital Clínico San Carlos, Madrid, Spain.
B
B
Fernández-Gutiérrez
S
S
de Miguel
C
C
Morado
C
C
Hernández-García
A
A
Bañares
J A
JA
Jover
D001402:B-Lymphocytes / Q000276:immunology*; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D017455:Receptors, IgE; D011493:Protein Kinase C