Activation of genetically major histocompatibility complex (MHC) class II-deficient B lymphocytes.
It has been suggested that MHC class II molecules can transduce signals required for B-cell activation. Enhancement or inhibition of B-cell stimulation by anti-MHC class II molecule antibodies has likewise been reported. The study of B cells from patients with a combined immune deficiency due to a defective expression of MHC class II genes provides a useful tool for approaching the functional role of B-cell HLA class II molecules. We have thus analyzed the specific and nonspecific, cognate and noncognate B-cell activation of genetically HLA class II-deficient lymphocytes. B lymphocytes from 14 tested patients were able to synthesize RNA following stimulation with ionomycin and phorbol myristate acetate or anti-mu antibodies and with mannan, a T cell-independent polysaccharidic antigen. They were also able to synthetize DNA following the addition of ionomycin and PMA or of anti-mu antibodies in the presence of recombinant interleukin 2. Pokeweed mitogen failed to induce B-lymphocyte terminal differentiation into immunoglobulin-producing cells in the presence of normal T lymphocytes, while a combination of anti-CD2 antibodies were capable of triggering IgG synthesis. B-cell activation, whatever the condition used, did not induce HLA class II expression. Mannan-specific T cell-dependent antibody production (IgM) was detected in 6 of 14 patients. Anti-influenza virus antibody production was always found absent. These results are compatible with the hypothesis that B-cell activation events that do not require a cognate interaction with T cells can occur in the absence of HLA class II molecule expression, while the absence of HLA class II molecule expression prevents T-B cognate interaction.
Durandy
A
A
Immunologie et Rhumatologie pédiatriques, INSERM U 132, Hôpital des Enfants-Malades, Paris, France.
Mangeney
M
M
Griscelli
C
C
Forveille
M
M
Le Deist
F
F
Fischer
A
A
D000293:Adolescent; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007223:Infant; D008213:Lymphocyte Activation; D008934:Mitogens / Q000276:immunology; D015398:Signal Transduction
D000949:Histocompatibility Antigens Class II; D008934:Mitogens