Analysis of immunoglobulin V genes suggests cutaneous marginal zone B-cell lymphomas recognise similar antigens.
Extranodal marginal zone B-cell lymphomas (EMZL) are thought to develop from reactive infiltrates that represent immune responses to external or auto-antigens. Except for gastric EMZL, the antigenic triggers of EMZL development are mostly unknown, although a subset of cutaneous EMZL have been associated with Borrelia burgdorferi infections. To further evaluate whether a common antigen may be promoting the development of cutaneous EMZL, the immunoglobulin heavy chain variable (V(H)) genes from eight USA cases were sequenced and analysed. All used V(H)3 family gene segments, with 2/8 using the same V3-30 segment, 2/8 using the closely related V3-30.3 or V3-33 segments, 6/8 containing mutations and 2/7 showing evidence of ongoing mutation. Many of the complimentarity-determining region 3s (CDR3s) also showed similarities in length and displayed conserved amino acid motifs in the non-templated areas between the diversity and joining segments. The use of similar V(H) gene segments and conserved CDR3 amino acid motifs suggests that some of these cutaneous EMZL may bind the same or similar antigen via their surface immunoglobulin receptor. Analysis of the somatic mutations present in many of the V(H) genes was also consistent with antigen directly stimulating the growth of cutaneous EMZL.
Bahler
David W
DW
Department of Pathology, University of Utah Medical Center, Salt Lake City, UT 84132, USA. dhb10@utah.edu
Kim
Bong K
BK
Gao
Aili
A
Swerdlow
Steven H
SH
D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D022801:Complementarity Determining Regions / Q000235:genetics*; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000276:immunology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D012878:Skin Neoplasms / Q000209:etiology* / Q000276:immunology
D000951:Antigens, Neoplasm; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains