Aberrant expression of immunoglobulin heavy chain genes in Epstein-Barr virus-negative, human immunodeficiency virus-related lymphoid interstitial pneumonia

Lab Invest. 2000 Dec;80(12):1891-903. doi: 10.1038/labinvest.3780199.


The two-step polymerase chain reaction (PCR) and sequencing analysis was used to analyze the immunoglobulin heavy chain variable (Ig V(H)) genes of open-chest biopsy or autopsy samples from five patients with Epstein-Barr virus-negative human immunodeficiency virus (HIV)-related lymphoid interstitial pneumonia (LIP), and the results were compared with those for Ig V(H) genes from five HIV-negative LIP patients. The findings of this study are consistent with the different immunological situations of HIV-related and HIV-negative LIP. (a) The Ig V(H)3 subgroup was underexpressed in three of five cases of HIV-related LIP. In contrast, none of the HIV-negative cases showed this abnormality. Because the Ig V(H)3 subgroup encodes the largest portion of Ig V(H) genes, a depletion of B cells expressing Ig V(H)3 genes reflects a major alteration in the B-cell compartment. (b) All HIV-related LIP cases demonstrated two or three oligoclonal populations. HIV-negative cases showed minor monoclonal or polyclonal populations, but not oligoclonal ones. These oligoclonal populations suggest the coexistence of several occult clonal B-cell populations in HIV-related LIP. (c) Some oligoclonal clones in HIV-related LIP showed mutated framework regions not demonstrated in HIV-negative clones. This degree of variation exceeds the usual mutation rate for frameworks, suggesting a role for framework residues in antigen binding. (d) The frequency of D-D fusions of minor oligoclonal clones (HIV-related LIP) is higher than that of minor monoclonal clones (HIV-negative LIP). Such D-D fusions may enhance the probability of expression of antibodies capable of binding HIV glycoproteins.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Female
  • Genes, Immunoglobulin*
  • HIV Infections / complications*
  • HIV Infections / immunology
  • Herpesvirus 4, Human
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin J-Chains / genetics
  • Infant
  • Lung Diseases / etiology*
  • Lung Diseases / genetics
  • Lung Diseases / immunology
  • Lung Diseases, Interstitial / etiology
  • Lung Diseases, Interstitial / genetics
  • Lung Diseases, Interstitial / immunology*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Probability


  • Immunoglobulin Heavy Chains
  • Immunoglobulin J-Chains