title: Effect of 12,13-phorbol dibutyrate and ionomycin on defective B cells in common variable immunodeficiency.
abstract: Secretion of IgM and IgG in vitro by B cells from patients with common variable immunodeficiency (CVI) has been used to classify the disease into three groups. On stimulation with anti-IgM and IL-2, group A patients' cells fail to secrete IgM or IgG, group B patients' cells secrete no IgG and significantly lower levels of IgM than normal cells, and group C patients' cells produce normal levels of both isotypes. Direct activation of protein kinase C using 12,13-phorbol dibutyrate and ionomycin followed by IL-2 or IL-4 has been reported to induce immunoglobulin secretion by normal human B cells. We therefore attempted to induce B cells from group A and group B CVI patients to secrete IgM and IgG after direct activation of protein kinase C together with IL-2 or IL-4. The data show that the failure of secretion of immunoglobulin by B cells from CVI patients could not be reversed using this approach. This finding suggests that the activation channel involving protein kinase C in B cells from CVI patients is not involved in the defect in cell differentiation.
authors.affiliation: Immunodeficiency Diseases Research Group, Clinical Research Centre, Harrow, England, U.K.
authors.forename: A
authors.initials: A
authors.lastname: Franz
authors.forename: A
authors.initials: A
authors.lastname: Bryant
authors.forename: A D
authors.initials: AD
authors.lastname: Webster
authors.forename: J
authors.initials: J
authors.lastname: Farrant
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004406:Dysgammaglobulinemia / Q000276:immunology*; D006801:Humans; D017099:IgG Deficiency; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000172:deficiency* / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D015847:Interleukin-4; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; D011493:Protein Kinase C