Synthesis and secretion of IgA, IgM, and IgG by peripheral blood mononuclear cells in human disease states, by isolated human intestinal mononuclear cells, and by human bone marrow mononuclear cells from ribs.
We have examined the secretion of IgA, IgM, and IgG by isolated human intestinal MNC, human bone marrow MNC from rib specimens, and peripheral blood MNC from patients with CD, UC, SLE, and HSP. "Normal" control intestinal MNC exhibited high spontaneous secretion of IgA, whereas intestinal MNC from UC and CD patients exhibited only modest increases in IgA secretion. Peripheral blood MNC from patients with CD, UC, SLE, and HSP exhibited markedly elevated spontaneous secretion of immunoglobulins in general and IgA in particular. Pure human bone marrow MNC exhibited high spontaneous secretion of IgA with modest amounts of IgG and normal IgM being secreted. The addition of PWM to cultures in which high spontaneous synthesis and secretion of immunoglobulins was seen, resulted in no further enhancement, and in some instances suppression, of antibody secretion. In patients with autoimmune disease, there appeared to be dual immunoregulatory defects, one involving a lack of normal T-suppressor cell functional capabilities for spontaneous antibody synthesis, and the other the presence of PWM activable T-suppressor cells. In human bone marrow, we have identified MNC that secrete suppressor factors in the presence of PWM and that are capable of inhibiting antibody synthesis and secretion. Column separation using Sephacryl S-300 revealed that the IgA secreted by "normal" control intestinal MNC is predominantly dimeric, whereas the IgA secreted by human bone marrow MNC is predominantly monomeric. Furthermore, mucosal MNC from patients with CD and uninvolved intestine from patients with UC exhibited patterns similar to control intestinal MNC, being predominantly dimeric IgA with some monomeric IgA secreted. By contrast, intestinal MNC from patients with UC had a decreased proportion of dimeric IgA and increased proportion of monomeric IgA, thus indicating that IgA precursor B-cells may have migrated into the intestine from extraintestinal sites, or that the normal dimeric IgA-secreting cells in the intestine had begun secreting increased proportion of monomeric IgA as well. These studies indicate that homing patterns and/or immunoregulation of IgA-secreting cells are altered in human intestine, bone marrow, and autoimmune disease states.
D000921:Antibody-Producing Cells / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells; D003093:Colitis, Ulcerative / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D006801:Humans; D011695:IgA Vasculitis / Q000276:immunology; D007070:Immunoglobulin A / Q000032:analysis / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D011487:Protein Conformation; D012272:Ribs
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins