Abnormalities in lymphocyte profile and specificity repertoire of patients with Waldenstrom's macroglobulinemia, multiple myeloma, and IgM monoclonal gammopathy of undetermined significance

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Abstract
The characteristics of T and B lymphocyte profile and B lymphocyte specificity repertoire were compared in patients with Waidenstrom'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 CDS (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 4B44 (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‐lg 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 fulfy 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 immunodeficency that is observed in these patients involves some abnormality in normal lymphocyte differentiation (is also present in MM).

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