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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
Author(s) -
Beiske Klaus,
Clark Edward A.,
Holte Harald,
Ledbetter Jeffrey A.,
Smeland Erlend B.,
Godal Tore
Publication year - 1988
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910420409
Subject(s) - antigen , cd20 , immunology , b cell , cell , pathology , medicine , biology , antibody , genetics
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 (slg). 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 G 1 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‐μ [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‐μ, 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‐μ 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.