Autoanti-red cell antibodies synthesized by patients with infectious mononucleosis utilize the VH4-21 gene segment.
A significant proportion of patients with B cell tumors secrete IgM mAb that recognize a carbohydrate autoantigen (li) on the red cell surface. The majority bear an idiotope (Id) that arises from heavy chains encoded by the VH4-21 gene segment, indicating unusual restriction of autoantibody specificity to a single VH gene. Polyclonal anti-li antibodies are also synthesized transiently by normal B cells following certain infections, and we have analyzed the role of the VH4-21 gene in encoding these antibodies. Levels of Id in sera of patients following infection with EBV or Mycoplasma pneumoniae were significantly raised (p < 0.01), and the Id-positive Ig reacted with patients' red cells. Id-positive B cell clones were established from four EBV-infected patients, and 6/6 of the IgM-Id agglutinated red cells. Nucleotide sequence analysis revealed involvement of the VH4-21 gene in all cases, with remarkably little change from the germ-line sequence. However, D segments were heterogeneous, and light chains differed. These results indicate that the same VH gene is used both by polyclonal autoantibodies produced in response to infection, and by B cell tumors. However, the lack of mutations would not appear to give an opportunity for Ag selection to drive affinity maturation of these autoantibodies.
Tenovus Laboratory, Southampton University Hospitals, UK.
C J
CJ
Chapman
M B
MB
Spellerberg
G A
GA
Smith
S J
SJ
Carter
T J
TJ
Hamblin
F K
FK
Stevenson
D000293:Adolescent; D000328:Adult; D000373:Agglutinins / Q000097:blood; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000096:biosynthesis*; D001483:Base Sequence; D002472:Cell Transformation, Viral; D003450:Cryoglobulins; D004912:Erythrocytes / Q000276:immunology*; D005803:Genes, Immunoglobulin; D004854:Herpesvirus 4, Human; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007130:Immunoglobulin Idiotypes / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics*; D007244:Infectious Mononucleosis / Q000276:immunology*; D008969:Molecular Sequence Data
D000373:Agglutinins; D001323:Autoantibodies; D003450:Cryoglobulins; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; C029443:cold agglutinins