title: Triggering of neoplastic B cells via surface IgM and the cell surface antigens CD20 and CDw40. Responses differ from normal blood B cells and are restricted to certain morphologic subsets.
abstract: By raising monoclonal antibodies (MAbs) against B cells, a number of cell surface molecules have recently been identified which after binding by their specific antibody can trigger B cells, either alone or in co-operation with antibodies to surface immunoglobulin (sIg). The anti-CD20 (Bp35) MAb IF5 can deliver a strong activation signal to resting normal B cells, and the anti-CDw40 (Bp50) MAb G28-5 can promote activated G1 B cells to enter S phase. These antibodies were tested for their functional effects in vitro on suspended cells from 17 follicle-center-cell (FCC) lymphomas, 5 cases of chronic lymphatic B-cell leukemia (B-CLL) and 8 cases of various histological types. Changes in cellular volume, RNA and DNA synthesis were compared with the results obtained with a polyclonal anti-mu [F(ab')2] antiserum, a MAb to surface IgM (AF6), 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and B-cell growth factor (low-molecular-weight BCGF). Our data reveal differences in the requirements for triggering of various B-cell subsets: cells from CLL responded strongly to TPA but not to anti-mu, which is a potent stimulator not only of normal B cells but also of cells from individual cases of FCC lymphomas. Our observations suggest that the differentiation stage of B-CLL cells is distinct from that of small resting B cells from peripheral blood. Centrocytic lymphomas could not be activated by any of the reagents. CD20-mediated triggering was seen in neoplastic B cells from only 4 of 30 cases, indicating that most B-cell neoplasias were not responsive to this activation pathway. In contrast, the anti-CDw40 MAb consistently stimulated DNA synthesis together with anti-mu or TPA in cells from FCC lymphomas, but not from CLL. Together, these results suggest that activation in different neoplastic B-cell subsets depends on distinct signal transduction mechanisms.
authors: Department of Pathology, Norwegian Radium Hospital, Oslo.
authors: K
authors: K
authors: Beiske
authors: E A
authors: EA
authors: Clark
authors: H
authors: H
authors: Holte
authors: J A
authors: JA
authors: Ledbetter
authors: E B
authors: EB
authors: Smeland
authors: T
authors: T
authors: Godal
mesh_terms: D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008213:Lymphocyte Activation; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology*; D010641:Phenotype; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D019013:CD40 Antigens; D007075:Immunoglobulin M; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D004247:DNA; D013755:Tetradecanoylphorbol Acetate