Synthesis of anti-acetylcholine receptor antibodies by CD5- B cells from peripheral blood of myasthenia gravis patients.
An increased frequency of CD5+ B cells (or, according to a new nomenclature, B1 cells) has been detected in the peripheral blood of a proportion of patients with myasthenia gravis (MG), as in some other autoimmune diseases. To elucidate the pathogenic significance of this B-cell subset in myasthenia gravis, mononuclear cells from the peripheral blood of six MG patients were separated into T and B lymphocytes by a magnetic cell separation procedure employing superparamagnetic microbeads (MACS). Subsequently, the B-cell fraction was depleted of CD5+ B cells in a second separation. The resulting purified CD5- B-cell fraction was cultured alone or with the addition of autologous T cells. Anti-acetylcholine receptor (AChR) synthesis by CD5- B cells in cultures with T cells was significantly increased by pokeweed mitogen (176 +/- 130 fmol/ml per week/2 x 10(5) B cells) compared with unfractionated cells (75 +/- 101) or CD5- B cells alone (19 +/- 4). These results demonstrate that in MG anti-AChR are synthesized, at least in part, by CD5- B cells which are dependent on T cells. Although this does not exclude the existence of AChR-specific CD5+ B cells, it provides evidence against a pivotal role of this B-cell subset in anti-AChR synthesis.
Heidenreich
F
F
Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany.
Jovin
T
T
D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001773:Blood Cells / Q000276:immunology*; D018956:CD5 Antigens / Q000032:analysis*; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009157:Myasthenia Gravis / Q000097:blood*; D011950:Receptors, Cholinergic / Q000276:immunology*
D001323:Autoantibodies; D018956:CD5 Antigens; D011950:Receptors, Cholinergic