Molecular characterization of a supratypic cross-reactive idiotype associated with IgM autoantibodies

J Immunol. 1991 Sep 15;147(6):2041-6.

Abstract

Neoplastic B cells from patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphomas (SLL) frequently express surface Ig reactive with the mouse mAb, Lc1. Raised against a human monoclonal IgM with rheumatoid factor activity, Lc1 detects a major cross-reactive Id (CRI) present on the H chain of many monoclonal IgM autoantibodies. In contrast to other major autoantibody-CRI investigated to date, we note that the Lc1-CRI is expressed by subpopulation of cells in the germinal centers, as well as in the mantle zones, of secondary human B cell follicles. To examine the molecular basis for Lc1 expression, we used the polymerase chain reaction to isolate the functionally rearranged Ig VH genes of monoclonal Lc1-reactive B cell populations from six unrelated patients with CLL or SLL. Although the neoplastic B cells from most patients with CLL or SLL express the CD5 surface differentiation Ag, the lymphoma cells from one patient with SLL were CD5-negative. We find that the Lc1-reactive cells from each cell population have Ig rearrangements involving a VH gene of the VH4 subgroup. However, the VH4 genes rearranged in different Lc1-reactive tumor populations may originate from at least two disparate germ-line VH4 genes. Also, in contrast to the CD5-positive tumor populations, we find evidence for intraclonal diversity in the functionally rearranged VH4 genes of the CD5-negative SLL. Collectively, this study discerns a degeneracy in the VH4 genes that can encode the Lc1 CRI, indicating the term "supratypic cross-reactive idiotype" may best describe the specificity of the Lc1 mAb. Also, this study suggests that expression of CD5 may delineate categories of B cell SLL that differ in their relative rates of constitutive Ig V gene somatic mutation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Anti-Idiotypic / immunology*
  • Autoantibodies / immunology*
  • Base Sequence
  • Cross Reactions
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genes, Immunoglobulin
  • Humans
  • Immunoglobulin Idiotypes / immunology*
  • Immunoglobulin M / immunology*
  • Immunoglobulin Variable Region / genetics
  • Leukemia, B-Cell / genetics
  • Molecular Sequence Data
  • Oligonucleotides / chemistry
  • Polymerase Chain Reaction

Substances

  • Antibodies, Anti-Idiotypic
  • Autoantibodies
  • Immunoglobulin Idiotypes
  • Immunoglobulin M
  • Immunoglobulin Variable Region
  • Oligonucleotides

Associated data

  • GENBANK/M64141
  • GENBANK/M64142
  • GENBANK/M64143
  • GENBANK/S55017
  • GENBANK/S55037
  • GENBANK/S55039
  • GENBANK/S55041
  • GENBANK/S55042
  • GENBANK/S55045
  • GENBANK/S55046