The immunology of AIDS-associated lymphomas

Lymphomas that occur in patients with human immunodeficiency virus (HIV) infection are predominantly of B-cell origin and subsets show evidence for Epstein-Barr virus (EBV) infection or chromosomal translocations in the c-myc locus. The only subset of lymphoma clearly related to the immunodeficiency caused by HIV infection (similar to transplantation-associated lymphomas) is the EBV+ primary central nervous system lymphoma. The systemic AIDS-related lymphomas (ARLs) represent a complex set of disease processes histologically categorized as large cell or small non-cleaved (Burkitt's-like) lymphomas. Molecular analyses of the ARLs have demonstrated polyclonal lymphomas as likely early representatives of monoclonal immunoglobulin (Ig)-expressing B-cell lymphomas. Variable region analysis of lymphoma-associated Ig has shown evidence for extensive somatic mutation with little evidence for appropriate affinity maturation. These observations suggest that abnormal control of B-cell maturation in response to polyclonal antigenic stimulation may play a central role in the pathogenesis of ARL. The recent finding of clonal HIV integrated within macrophages in a subset of early lymphomas also provides evidence for abnormalities outside the B-cell compartment playing roles in this disease. Overall, ARLs generally appear to be outgrowths of antigen-driven B-cells with significant growth control influence provided by abnormal T-cell and antigen-presenting cell processes.