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.
Sarfati M , Delespesse G . Possible role of human lymphocyte receptor for IgE (CD23) or its soluble fragments in the in vitro synthesis of human IgE . J Immunol1988; 141: 2195-2199 .
7.
Swendeman S , Thorley-Lawson DA . The activation antigen BLAST-2, when shed, is an autocrine BCGF for normal and transformed B cells . EMBO J1987; 6: 1736-1642 .
8.
Gordon J , Rowe M , Walker L , Guy G . Litigation of the CD23, p45 (BLAST-2, EBVCS) antigen triggers the cell-cycle progression of activated B lymphocytes . Eur J Immunol1986; 16: 1075-1079 .
9.
Kintner C , Sudgen B . Identification of antigenic determinants unique to the surfaces of cells transformed by Epstein Barr virus . Nature1981; 294: 458-460 .
10.
Thorley-Lawson DA , Nadler LM , Bhan AK , Schooley RT . Blast-2 (EBVCS), an early cell surface marker on human B cell activation is superinduced by EBV . J Immunol1985; 134: 3007-3012 .
11.
Crow MK , Jover JA , Friedman S . Direct T helper-B cell interactions induce an early B cell activation antigen . J Exp Med1986; 164: 1760-1772 .
12.
De France T , Aubry JP , Rousset F , Vanbervliet B , Bonnefoy JY , Arai N , Takebe Y , Yokota T , Lee F , Arai K , DeVries J , Banchereau J . Human recombinant interleukin 4 induces Fc receptors (CD23) on normal human B lymphocytes . J Exp Med1987; 165: 1459-1467 .
13.
Aubry JP , Pochon S , Graber P , Jansen KU , Bonnefoy JY . CD21 is a ligand for CD23 and regulates IgE production . Nature1992; 258: 505-507 .
14.
Kumagai S , Ishida H , Iwai K , Tsubata T , Umehara H , Ozaki S , Suginoshita T , Araya S , Imura H . Possible different mechanisms of B cell activation in systemic lupus erythematosus and rheumatoid arthritis: opposite expression of low-affinity receptors for IgE (CD23) on their peripheral B cells . Clin Exp Immunol1989; 78: 348-353 .
15.
Chomarat P , Briolay J , Banchereau J , Miossec P . Increased production of soluble CD23 in rheumatoid arthritis, and its regulation by interleukin-4 . Arthritis Rheum.1993; 36: 234-242 .
16.
Fernández-Gutiérrez B , Hernández-García C , Bañares AA , Jover JA . CD23 hyperexpression in Rheumatoid Arthritis: Evidence for a B cell hyperresponsiveness to cognate and non-cognate T-cell signals . Clin Immunol Immunopathol1994; 72: 321-327 .
17.
López-Cabrera M , Santís AG , Ferńndez-Ruíz E , Blacher R , Eash F , Sánchez-Mateos P , Sánchez-Madrid F . Molecular cloning, expression, and chromosomal localization of the human earliest lymphocyte activation antigen AIM/CE69, a new member of the C-type animal lectin superfamily of signal transmitting receptors . J Exp Med1993; 178: 537-547 .
18.
Hamann J , Fiebig H , Strauss M . Expression and cloning of the early activation antigen CD69, a type II integral membrane protein with a C-type lectin domain . J Immunol1993; 150: 4920-4927 .
19.
Cebrian M , Miguel Redondo J , Lopez-Rivas A , Rodriguez-Tarduch G , De Landazuri MOP , Sanchez-Madrid F . Expression and function of AIM, an activation inducer molecule of human lymphocytes, is dependent on the activation of protein kinase C . Eur J Immunol1989; 19: 809-815 .
20.
Risso A , Smilovich D , Capra MC , BaldisarroI , Yan G , Bargellesi A , Cosulich ME . CD69 in resting and activated T lymphocytes. Its association with a GTP binding protein and biochemical requirements for its expression . J Immunol1991; 146: 4105-4114 .
21.
Testi R , Phillips JH , Lanier LL . Leu 23 induction as an early marker of functional CD3=T cell antigen receptor triggering . J Immunol1989; 142: 1854-1860 .
22.
Verwilghen J , Vandenberghe P , Wallays G , de Boer M , Anthony N , Panayi GS , Ceuppens JL . Simultaneous ligation of CD5 and CD28 on resting T lymphocytes induces T cell activation in the absence of T cell receptor/CD3 occupancy . J Immunol1993; 150: 835-846 .
23.
Cebrián M , Yagäe E , RincónM , López-Botet M , Portiz de Landázuri M , Sanchez-Madrid F . Triggering of T cell proliferation through AIM, an activation inducer molecule expressed on activated human lymphocytes . J Exp Med1988; 168: 1621-1637 .
24.
Hara T , Jung LKL , Bjorndahl JM , Fu SM . Human T cell activation. III. Rapid induction of a phosphorilated 28 kDa=32 kD disulfide-linked early activation antigen (EA 1) by 12-o-tetradecanoyl phorbol-13-acetate, mitogens and antigens . J Exp Med1986; 164: 1988-2005 .
25.
Fernández-Gutiérrez B , Hernández-García C , Bañares AA , Jover JA . Characterization and regulation of CD69 expression on rheumatoid arthritis synovial fluid T cells . J Rheumatol1995; 22: 413-420 .
26.
Hernández-García C , Fernández-Gutírrez B , Morado IC , Bañares AA , Jover JA . CD69 activation pathway in Rhematoid Arthritis synovial fluid T cells . Arthritis Rhem1996; 39: 1277-1286 .
27.
Serra JA , Fernández-Gutírrez B , Hernández-García C , Vidan M , Ribera JM , Bañares A , Jover JA . Early T cell activation in elderly humans . Age and Ageing1996; 25: 470-478 .
28.
Lederman SM , Yellin MH , Krichevsky A , Belko J , Lee JJ , Chess L . Identification of a novel surface protein on activated CD4 / T cells that induces contact dependent B cell differentiation (help) . J Exp Med1992; 175: 1901-1907 .
29.
Aruffo A , Farryngton M , Hollenbaugh D , Lui X , Milatovich A , Nonoyama S , Bajorath J , Grosmaire LS , Stenkamp R , Neubauer M , Roberts RL , Noelle RJ , Ledbetter JA , Francke U , Ochs HD . The CD40 ligand, gp39 is defective in activated T cells from patients with X-linked hyper Ig-M syndrome . Cell1993; 72: 291-300 .
30.
Lederman S , Yellin MJ , Inghirami G , Lee JJ , Knowles DM , Chess L . Molecular interactions mediating T-B lymphocyte collaboration in human lymphoyd follicles . J Immunol1992; 149: 3817-3826 .
31.
Mohan C , Shi Y , Laman JD , Datta SK . Interaction between CD40 and its ligand gp39 in the development of murine lupus nephritis . J Immunol1995; 154: 1470-1480 .
32.
Desai-Metha A , Lu L , Ramsey-Goldman R , Datta SK . Hyperexpression of CD40 ligand by B and T cells in human lupus and its role in pathogenic autoantibody production . J Clin Invest1996; 97: 2063-2073 .
33.
Koshy M , Berger, D , Crow MK . Increased expression CD40 ligand on Systemic Lupus Erythematosus lymphocytes . J Clin Invest1996; 98: 826-837 .
34.
Tan EM , Cohen AS , Fries JF , Masi AT , McShane DJ , Rothfield NF , Shaller JG , Talal N , Winchester RJ . The 1982 revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum1982; 25: 1271-1277 .
35.
Hahn BH . Management of Systemic Lupus Erythematosus. In: Kelly WN , Harris Jr. ED , Ruddy S , Slegde CB (eds.). Textbook of Rheumathology. WB Saunders Company: Philadelphia , 1993, pp 1043-1056.
36.
Liang MH , Socher SA , Larson MG , Schur PH . Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus . Arthritis Rheum1989; 321107-1118 .
37.
Gottlieb AB , Fu SM , Yu DTY , Wang CY , Halper JP , Kunkel HG . The nature of the stimulatory cell in human allogeneic and autologous MCL reactions; role of isolated IgM-bearing B cells . J Immunol.1979; 123: 1497-1502 .
38.
Lane P , Traunnecker A , Hubele S , Inui S , Lanzavecchia A , Gray D . Activated human T cells express a ligand for the human B-cell associated antigen CD40 which participates in T-cell dependent activation of B lymphocytes . Eur J Immunol1992; 22: 2573-2578 .
39.
Friedman SM , Jover JA , Chartash EK , Crow MK . Antigen-specific, MHC nonrestricted T helper cell-induced B cell activation . J Exp Med1986; 164: 1773-1778 .
40.
Jover JA , Chartash EK , Kushner B , Friedman S , Crow MK . T helper cell-induced CD23 (BLAST-2) expression: an activation marker for the high density fraction of human B cells . Clin Immunol Immunopathol1989; 53: 99-112 .
41.
Crow MK , Kushner B , Jover JA , Friedman S , Mechanic SE , Stohl W . Human peripheral blood T helper cell-induced B cell activation results in B cell surface expression of the CD23 (Blast-2) antigen . Cell Immunol1989; 121: 99-112 .
42.
Kuhn R , Rajewsky K , Muller W . Generation and analysis of interleukin-4 deficient mice . Science1991; 254: 707-710 .
43.
Cambier JC , Pleiman CM , Clark MR . Signal transduction by the B cell antigen receptor and its coreceptors . Annu Rev Immunol1994; 12: 457-486 .
44.
McInnes IB , Leung BP , Sturrock RD , Field M , Liew FY . Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-a production in rheumatoid arthritis . Nat Med1997; 3.2: 189-195 .
45.
Huang YP , Perrin LH , Miescher PA , Zubler RH . Correlation of T and B cell activities in vitro and serum IL-2 levels in Systemic Lupus Erythematosus . J Immunol1986; 141: 827-833 .
46.
Bowen F , Haluskey J , Quill H . Altered CD40 ligand induction in tolerant T lymphocytes . Eur J Immunol1995; 25: 2830-2834 .
