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

The two-step polymerase chain reaction (PCE) and sequencing analysis was us ed to analyze the immunoglobulin heavy chain variable (Ig V-H) genes of ope n-chest biopsy or autopsy samples from five patients with Epstein-Barr viru s-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 consis tent with the different immunological situations of HIV-related and HIV-neg ative LIP. (a) The Ig V(H)3 subgroup was underexpressed in three of five ca ses 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 show ed minor monoclonal or polyclonal populations, but not oligoclonal ones. Th ese oligoclonal populations suggest the coexistence of several occult clona l B-cell populations in HIV-related LIP. (c) Some oligoclonal clones in HIV -related LIP showed mutated framework regions not demonstrated in HIV-negat ive clones. This degree of variation exceeds the usual mutation rate for fr ameworks, 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.