Autoantibody-associated cross-reactive idiotype-bearing human B lymphocytes: distribution and characterization, including Ig VH gene and CD5 antigen expression.
Monoclonal antibodies (MoAbs) specific for autoantibody associated cross-reactive idiotypes (CRIs) frequently recognize the Igs of neoplastic B cells in patients with chronic lymphocytic leukemia (CLL) and/or Waldenstrom's macroglobulinemia. Very little is known regarding the normal B cells expressing CRIs (CRI-positive B cells). Using a variety of MoAbs against CRIs we investigated the distribution and topographic localization of CRI-positive B cells in normal adult human lymphoid tissues. We found that CRI-positive B cells represent a significant B-cell subpopulation expressing surface IgM (greater than 90%), IgG (approximately 5%), or IgA (approximately 2%). CRI-positive B cells are homogeneously distributed throughout all lymphoid tissues, accounting for 10% to 15% of all B lymphocytes, with the exception of the thymus, in which they represent the predominant B cell population. Immunophenotypic studies showed (1) that a small subpopulation (3.7% +/- 0.8%) of CRI-positive B cells are activated in vivo, based on CD25 and CD38 antigen expression; and (2) that approximately 50% of CRI-positive B cells express the 67-Kd pan-T-lymphocyte CD5 antigen, suggesting that the CRI-positive B-cell subset and the recently described CD5-positive B-cell subset are closely related. This hypothesis is supported by the fact that CRI-positive B cells produce oligo or polyreactive Igs, which are a characteristic feature of CD5-positive B cells, and also by the fact that both B-cell subpopulations appear to use similar and restricted Ig VH gene family members.
Inghirami
G
G
Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
Foitl
D R
DR
Sabichi
A
A
Zhu
B Y
BY
Knowles
D M
DM
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis*; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens; D003429:Cross Reactions / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007075:Immunoglobulin M / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001323:Autoantibodies; D018956:CD5 Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M