Production of autoantibodies by CD5-expressing B lymphocytes from patients with chronic lymphocytic leukemia

doi:10.1084/jem.169.1.255

This Article

	Full Text (PDF, 889K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Sthoeger, Z. M.
	Articles by Chiorazzi, N.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Sthoeger, Z. M.
	Articles by Chiorazzi, N.


Social Bookmarking

	What's this?

ARTICLES

Production of autoantibodies by CD5-expressing B lymphocytes from patients with chronic lymphocytic leukemia

ZM Sthoeger, M Wakai, DB Tse, VP Vinciguerra, SL Allen, DR Budman, SM Lichtman, P Schulman, LR Weiselberg and N Chiorazzi
Department of Medicine, North Shore University Hospital, Manhasset, New York 11030.

CD5-expressing B lymphocytes from patients with selected chronic lymphoproliferative disorders were used to determine whether monoclonal populations of CD5+ human B cells produce autoantibodies. CD5+ B cells from 19 patients with chronic lymphocytic leukemia (CLL) and one with diffuse well-differentiated lymphocytic lymphoma (DWDL) were cultured, with and without mitogenic stimulation, to obtain Ig from these cells. 17 of the 20 samples produced Ig in vitro. mAb from nine of the 17 patients were reactive with either IgG, ssDNA, or dsDNA. In every instance, the autoantibodies displayed monotypic L chain usage that correlated precisely with the L chain expressed on the CD5+ leukemic B cell surface. These monoclonal autoantibodies varied in their degree of antigenic specificity; some were quite specific, reacting with only one antigen, whereas others were polyspecific, reacting with two or all three autoantigens tested. Three features distinguish these autoantibodies from those observed in prior studies of CD5+ B cells. First, they are clearly the products of monoclonal populations of CD5+ cells; second, several react with dsDNA, a specificity not previously reported and often seen in association with significant autoimmune disorders; and third, two of the monoclonal autoantibodies secreted by the CD5+ clones were of the IgG class. Although not all of the Ig- producing, CD5-expressing clones elaborated mAbs reactive with the autoantigens tested, greater than 50% did. It is possible that with a broader autoantigenic panel or with larger quantities of CLL/DWDL- derived Ig, even more autoantibody-producing clones might be identified. These studies may have important implications for the antigenic specificity of subsets of human B lymphocytes as well as for lymphoproliferative and autoimmune disorders in general.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Seiler, T., Woelfle, M., Yancopoulos, S., Catera, R., Li, W., Hatzi, K., Moreno, C., Torres, M., Paul, S., Dohner, H., Stilgenbauer, S., Kaufman, M. S., Kolitz, J. E., Allen, S. L., Rai, K. R., Chu, C. C., Chiorazzi, N. (2009). Characterization of structurally defined epitopes recognized by monoclonal antibodies produced by chronic lymphocytic leukemia B cells. Blood 114: 3615-3624 [Abstract] [Full Text]
Galletti, J., Canones, C., Morande, P., Borge, M., Oppezzo, P., Geffner, J., Bezares, R., Gamberale, R., Giordano, M. (2008). Chronic Lymphocytic Leukemia Cells Bind and Present the Erythrocyte Protein Band 3: Possible Role as Initiators of Autoimmune Hemolytic Anemia. J. Immunol. 181: 3674-3683 [Abstract] [Full Text]
Widhopf, G. F. II, Goldberg, C. J., Toy, T. L., Rassenti, L. Z., Wierda, W. G., Byrd, J. C., Keating, M. J., Gribben, J. G., Rai, K. R., Kipps, T. J. (2008). Nonstochastic pairing of immunoglobulin heavy and light chains expressed by chronic lymphocytic leukemia B cells is predicated on the heavy chain CDR3. Blood 111: 3137-3144 [Abstract] [Full Text]
Cutrona, G., Colombo, M., Matis, S., Fabbi, M., Spriano, M., Callea, V., Vigna, E., Gentile, M., Zupo, S., Chiorazzi, N., Morabito, F., Ferrarini, M. (2008). Clonal heterogeneity in chronic lymphocytic leukemia cells: superior response to surface IgM cross-linking in CD38, ZAP-70-positive cells. haematol 93: 413-422 [Abstract] [Full Text]
Volkheimer, A. D., Weinberg, J. B., Beasley, B. E., Whitesides, J. F., Gockerman, J. P., Moore, J. O., Kelsoe, G., Goodman, B. K., Levesque, M. C. (2007). Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification. Blood 109: 1559-1567 [Abstract] [Full Text]
Stamatopoulos, K., Belessi, C., Moreno, C., Boudjograh, M., Guida, G., Smilevska, T., Belhoul, L., Stella, S., Stavroyianni, N., Crespo, M., Hadzidimitriou, A., Sutton, L., Bosch, F., Laoutaris, N., Anagnostopoulos, A., Montserrat, E., Fassas, A., Dighiero, G., Caligaris-Cappio, F., Merle-Beral, H., Ghia, P., Davi, F. (2007). Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: pathogenetic implications and clinical correlations. Blood 109: 259-270 [Abstract] [Full Text]
Yan, X.-j., Albesiano, E., Zanesi, N., Yancopoulos, S., Sawyer, A., Romano, E., Petlickovski, A., Efremov, D. G., Croce, C. M., Chiorazzi, N. (2006). B cell receptors in TCL1 transgenic mice resemble those of aggressive, treatment-resistant human chronic lymphocytic leukemia. Proc. Natl. Acad. Sci. USA 103: 11713-11718 [Abstract] [Full Text]
Yee, K. W. L., O'Brien, S. M. (2006). Chronic Lymphocytic Leukemia: Diagnosis and Treatment. Mayo Clin Proc. 81: 1105-1129 [Abstract] [Full Text]
Thorselius, M., Krober, A., Murray, F., Thunberg, U., Tobin, G., Buhler, A., Kienle, D., Albesiano, E., Maffei, R., Dao-Ung, L.-P., Wiley, J., Vilpo, J., Laurell, A., Merup, M., Roos, G., Karlsson, K., Chiorazzi, N., Marasca, R., Dohner, H., Stilgenbauer, S., Rosenquist, R. (2006). Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status. Blood 107: 2889-2894 [Abstract] [Full Text]
Stamatopoulos, K., Belessi, C., Hadzidimitriou, A., Smilevska, T., Kalagiakou, E., Hatzi, K., Stavroyianni, N., Athanasiadou, A., Tsompanakou, A., Papadaki, T., Kokkini, G., Paterakis, G., Saloum, R., Laoutaris, N., Anagnostopoulos, A., Fassas, A. (2005). Immunoglobulin light chain repertoire in chronic lymphocytic leukemia. Blood 106: 3575-3583 [Abstract] [Full Text]
Bende, R. J., Aarts, W. M., Riedl, R. G., de Jong, D., Pals, S. T., van Noesel, C. J.M. (2005). Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity. JEM 201: 1229-1241 [Abstract] [Full Text]
Vuillier, F., Dumas, G., Magnac, C., Prevost, M.-C., Lalanne, A. I., Oppezzo, P., Melanitou, E., Dighiero, G., Payelle-Brogard, B. (2005). Lower levels of surface B-cell-receptor expression in chronic lymphocytic leukemia are associated with glycosylation and folding defects of the {micro} and CD79a chains. Blood 105: 2933-2940 [Abstract] [Full Text]
Chiorazzi, N., Rai, K. R., Ferrarini, M. (2005). Chronic Lymphocytic Leukemia. NEJM 352: 804-815 [Full Text]
Widhopf, G. F. II, Rassenti, L. Z., Toy, T. L., Gribben, J. G., Wierda, W. G., Kipps, T. J. (2004). Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins. Blood 104: 2499-2504 [Abstract] [Full Text]
Messmer, B. T., Albesiano, E., Efremov, D. G., Ghiotto, F., Allen, S. L., Kolitz, J., Foa, R., Damle, R. N., Fais, F., Messmer, D., Rai, K. R., Ferrarini, M., Chiorazzi, N. (2004). Multiple Distinct Sets of Stereotyped Antigen Receptors Indicate a Role for Antigen in Promoting Chronic Lymphocytic Leukemia. JEM 200: 519-525 [Abstract] [Full Text]
Stevenson, F. K., Caligaris-Cappio, F. (2004). Chronic lymphocytic leukemia: revelations from the B-cell receptor. Blood 103: 4389-4395 [Abstract] [Full Text]
Widhopf, G. F. II, Brinson, D. C., Kipps, T. J., Tighe, H. (2004). Transgenic Expression of a Human Polyreactive Ig Expressed in Chronic Lymphocytic Leukemia Generates Memory-Type B Cells That Respond to Nonspecific Immune Activation. J. Immunol. 172: 2092-2099 [Abstract] [Full Text]
Albesiano, E., Messmer, B. T., Damle, R. N., Allen, S. L., Rai, K. R., Chiorazzi, N. (2003). Activation-induced cytidine deaminase in chronic lymphocytic leukemia B cells: expression as multiple forms in a dynamic, variably sized fraction of the clone. Blood 102: 3333-3339 [Abstract] [Full Text]
Keating, M. J., Chiorazzi, N., Messmer, B., Damle, R. N., Allen, S. L., Rai, K. R., Ferrarini, M., Kipps, T. J. (2003). Biology and Treatment of Chronic Lymphocytic Leukemia. ASH Education Book 2003: 153-175 [Abstract] [Full Text]
Gary-Gouy, H., Harriague, J., Bismuth, G., Platzer, C., Schmitt, C., Dalloul, A. H. (2002). Human CD5 promotes B-cell survival through stimulation of autocrine IL-10 production. Blood 100: 4537-4543 [Abstract] [Full Text]
Rosenwald, A., Alizadeh, A. A., Widhopf, G., Simon, R., Davis, R. E., Yu, X., Yang, L., Pickeral, O. K., Rassenti, L. Z., Powell, J., Botstein, D., Byrd, J. C., Grever, M. R., Cheson, B. D., Chiorazzi, N., Wilson, W. H., Kipps, T. J., Brown, P. O., Staudt, L. M. (2001). Relation of Gene Expression Phenotype to Immunoglobulin Mutation Genotype in B Cell Chronic Lymphocytic Leukemia. JEM 194: 1639-1648 [Abstract] [Full Text]
Bernal, A., Pastore, R. D., Asgary, Z., Keller, S. A., Cesarman, E., Liou, H.-C., Schattner, E. J. (2001). Survival of leukemic B cells promoted by engagement of the antigen receptor. Blood 98: 3050-3057 [Abstract] [Full Text]
Meffre, E., Chiorazzi, M., Nussenzweig, M. C. (2001). Circulating Human B Cells That Express Surrogate Light Chains Display a Unique Antibody Repertoire. J. Immunol. 167: 2151-2156 [Abstract] [Full Text]
Meffre, E., Catalan, N., Seltz, F., Fischer, A., Nussenzweig, M. C., Durandy, A. (2001). Somatic Hypermutation Shapes the Antibody Repertoire of Memory B Cells in Humans. JEM 194: 375-378 [Abstract] [Full Text]
Caligaris-Cappio, F., Hamblin, T. J. (1999). B-Cell Chronic Lymphocytic Leukemia: A Bird of a Different Feather. JCO 17: 399-399 [Abstract] [Full Text]
Hamano, Y., Hirose, S., Ida, A., Abe, M., Zhang, D., Kodera, S., Jiang, Y., Shirai, J., Miura, Y., Nishimura, H., Shirai, T. (1998). Susceptibility Alleles for Aberrant B-1 Cell Proliferation Involved in Spontaneously Occurring B-Cell Chronic Lymphocytic Leukemia in a Model of New Zealand White Mice. Blood 92: 3772-3779 [Abstract] [Full Text]
Matolcsy, A., Casali, P., Nador, R. G., Liu, Y.-F., Knowles, D. M. (1997). Molecular Characterization of IgA- and/or IgG-Switched Chronic Lymphocytic Leukemia B Cells. Blood 89: 1732-1739 [Abstract] [Full Text]
Foon, K. A., Rai, K. R., Gale, R. P. (1990). Chronic Lymphocytic Leukemia: New Insights into Biology and Therapy. ANN INTERN MED 113: 525-539 [Abstract]