title: IL-4 rescues surface IgM expression in chronic lymphocytic leukemia.
abstract: Chronic lymphocytic leukemia (CLL) cells express poor levels of surface immunoglobulin (sIg), and many are minimally activated or anergic in response to B-cell receptor (BCR) crosslinking in vitro. Paradoxically, CLL cells in patients are highly activated through BCR signaling and expand in proliferation centers, suggesting that the function of sIg signaling is rescued. Here, we find that, compared with normal naïve B cells, CLL cells express a low level of total CD79b protein but normal levels of CD79a and IgM protein. Association of both CD79a and CD79b to IgM is markedly reduced. We further find that interleukin-4 (IL-4) markedly rescues CD79b and sIgM protein in CLL samples. These changes significantly enhance signaling in response to BCR crosslinking. Furthermore, we find that these changes are more pronounced in immunoglobulin heavy chain variable (IGHV)-unmutated CLL cells than IGHV-mutated CLL cells. The results described herein reveal that reduced sIgM is due to low expression of total CD79b protein in CLL cells. IL-4 substantially restores CD79b protein expression, sIgM expression, and BCR signaling.
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, NY;
authors.forename: Benchang
authors.identifier: 0000-0002-8590-0635
authors.initials: B
authors.lastname: Guo
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, NY;
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, NY; Department of Medicine, North Shore University Hospital, Manhasset, NY; Department of Medicine, and Department of Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY.
authors.forename: Nicholas
authors.identifier: 0000-0003-1023-6650
authors.initials: N
authors.lastname: Chiorazzi
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, NY; Department of Medicine, and Department of Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Rothstein
mesh_terms: D051925:CD79 Antigens / Q000276:immunology; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D051925:CD79 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; C508598:IL4 protein, human; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D009363:Neoplasm Proteins; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4