Defective T Cell-Mediated, Isotype-Specific Immunoglobulin Regulation in B Cell Chronic Lymphocytic Leukemia

• Published in: Blood Vol. 71; no. 4; pp. 1012 - 1020
• Main Authors: Moore, Jonni S., Prystowsky, Michael B., Hoover, Richard G., Besa, Emmanuel C., Nowell, Peter C.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.04.1988; The Americain Society of Hematology
• Subjects: Adult; Aged; Antigens, CD; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Biological and medical sciences; Chromatography, High Pressure Liquid; Female; Hematologic and hematopoietic diseases; Humans; Immunoglobulin A - biosynthesis; Immunoglobulin A - metabolism; Immunoglobulin A - physiology; Immunoglobulin A, Secretory - biosynthesis; Immunoglobulin Isotypes - biosynthesis; Immunoglobulin Isotypes - physiology; Immunologic Deficiency Syndromes - blood; Immunologic Deficiency Syndromes - immunology; Leukemia, Lymphoid - blood; Leukemia, Lymphoid - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocyte Count; Lymphocyte Activation; Lymphokines - biosynthesis; Lymphokines - isolation & purification; Lymphokines - physiology; Male; Medical sciences; Middle Aged; Prostatic Secretory Proteins; Receptors, Fc - analysis; Suppressor Factors, Immunologic - biosynthesis; Suppressor Factors, Immunologic - immunology; T-Lymphocytes - classification; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Human; IgA; Immunoglobulins; Chronic lymphocytic leukemia; Immunological investigation; Isotypy; Pathogenesis; Hemopathy; Immune regulation; B-Lymphocyte; T»-Lymphocyte
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V71.4.1012.1012

The consistent occurrence of T cell abnormalities in patients with B cell chronic lymphocytic leukemia (B-CLL) suggests that the non-neoplastic host T cells may be involved in the pathogenesis of this B cell neoplasm. Because potential defects of immunoglobulin regulation are evident in B-CLL patients, we investigated one aspect of this by studying the T cell-mediated immunoglobulin isotype-specific immunoregulatory circuit in B-CLL. The existence of class-specific immunoglobulin regulatory mechanisms mediated by Fc receptor-bearing T cells (FcR + T) through soluble immunoglobulin binding factors (IgBFs) has been well established in many experimental systems. IgBFs can both suppress and enhance B cell activity in an isotype-specific manner. We investigated the apparently abnormal IgA regulation in a B-CLL patient (CLL249) whose B cells secrete primarily IgA in vitro. Enumeration of FcR+ T cells showed a disproportionate increase in IgA FcR + T cells in the peripheral blood of this patient. Our studies showed that the neoplastic B cells were not intrinsically unresponsive to the suppressing component of IgABF produced from normal T cells, but rather the IgABF produced by the CLL249 host T cells was defective. CLL249 IgABF was unable to suppress IgA secretion by host or normal B cells and enhanced the in vitro proliferation of the host B cells. Size fractionation of both normal and CLL249 IgABF by gel-filtration highperformance liquid chromatography (HPLC) demonstrated differences in the ultraviolet-absorbing components of IgABF obtained from normal T cells v that from our patient with defective IgA regulation. Such T cell dysfunction may not be restricted to IgA regulation, since we have found similar expansion of isotype-specific FcR + T cells associated with expansion of the corresponding B cell clone in other patients with B-CLL. These data suggest that this T cell-mediated regulatory circuit could be significantly involved in the pathogenesis of B-CLL.© 1988 by Grune & Stratton, Inc. 0006-4971/88/7104-0055$3.00/0