title: Abnormalities in lymphocyte profile and specificity repertoire of patients with Waldenstrom's macroglobulinemia, multiple myeloma, and IgM monoclonal gammopathy of undetermined significance.
abstract: The characteristics of T and B lymphocyte profile and B lymphocyte specificity repertoire were compared in patients with Waldenstrom's macroglobulinemia (WM), IgM monoclonal gammopathy of undetermined significance (IgM MGUS), multiple myeloma (MM), and age-matched normal subjects. Patients with MM had both significantly reduced frequency and number of sIg+ (surface Ig) B cells, whereas patients with WM and IgM MGUS had a reduced frequency but normal numbers of sIg+ B cells in circulation as detected in a capping assay. WM was distinguished by the large numbers of cells in the peripheral blood lymphocyte (PBL) pool that expressed CD9 (BA-2) and CD24 (BA-1) and were monoclonal, based on light chain analysis using flow cytometry. The profile of T lineage cells showed that the ratio of CD4:CD8 was significantly reduced in both MM and WM due to a reduction in the CD4 set. The CD4+ cells were qualitatively abnormal as well, with an enriched proportion of the 4B4+ (CDw29) subset and decreased proportion of the Lp220+ (CD45R) subset. This appeared to be an effect of the disease process on the relatively immature Lp220+ set. From clonal analysis, those patients with WM or IgM MGUS (unlike MM patients) did not exhibit enhanced reactivity with auto-Ig determinants, and most WM patients (7/8) and half of the IgM MGUS patients (3/6) did not have enriched proportions of B cells reactive to tetanus toxoid (TT). The TT-specific B cells in both WM and IgM MGUS, in contrast to MM, appeared fully functional in secretion of anti-TT IgM in vivo. We speculate that the more severe immunodeficiency in MM may be controlled or exacerbated by the presence of an anti-Ig network. The absence of this network in WM allows a relatively more effective immune response, but the immunodeficiency that is observed in these patients involves some abnormality in normal lymphocyte differentiation (is also present in MM).
authors.affiliation: Department of Immunology, University of Alberta, Edmonton, Canada.
authors.forename: L M
authors.initials: LM
authors.lastname: Pilarski
authors.forename: E J
authors.initials: EJ
authors.lastname: Andrews
authors.forename: H M
authors.initials: HM
authors.lastname: Serra
authors.forename: J A
authors.initials: JA
authors.lastname: Ledbetter
authors.forename: B A
authors.initials: BA
authors.lastname: Ruether
authors.forename: M J
authors.initials: MJ
authors.lastname: Mant
mesh_terms: D000917:Antibody Formation; D001402:B-Lymphocytes / Q000145:classification; D002472:Cell Transformation, Viral; D004854:Herpesvirus 4, Human; D006801:Humans; D007075:Immunoglobulin M; D008214:Lymphocytes / Q000145:classification; D009101:Multiple Myeloma / Q000473:pathology*; D010265:Paraproteinemias / Q000473:pathology*; D012016:Reference Values; D013601:T-Lymphocytes / Q000145:classification; D008258:Waldenstrom Macroglobulinemia / Q000473:pathology*
chemical_list: D007075:Immunoglobulin M