title: B lymphocytes in the normal brain: contrasts with HIV-associated lymphoid infiltrates and lymphomas.
abstract: In recent years evidence has accumulated which suggests that the brain may not be the immunologically privileged site it was once considered to be. It is now widely accepted that T lymphocytes perform surveillance functions in normal brain parenchyma. However, as yet there are no reports of B lymphocytes entering brain parenchyma in the healthy state. This study aimed to determine first the prevalence of B lymphocytes in normal brain, and subsequently whether advancing HIV infection led to changes in the brain B lymphocyte population, which might contribute to the increased risk of lymphoma seen in AIDS. Our results show that B lymphocytes do enter all parts of the normal human brain in very low numbers and that the B lymphocytes within the brain parenchyma display an activated (CD23 positive) phenotype. In contrast, intravascular B lymphocytes have a much lower expression of activation markers. B lymphocytes were found in increased numbers in both the brain parenchyma and perivascular spaces of pre-AIDS brains. However, brains from the majority of AIDS subjects, including those with primary CNS lymphoma (PCNSL) (outside the area of neoplastic involvement) contained fewer B lymphocytes than normal or pre-symptomatic HIV-infected brains. A subset of AIDS brains, previously shown to have pleomorphic lymphoid infiltrates in the perivascular spaces, had significantly increased numbers of B lymphocytes in both the brain parenchyma and perivascular spaces. Virtually all AIDS-related PCNSL are known to be Epstein-Barr Virus (EBV) positive, in contrast to non-HIV PCNSL and non-CNS AIDS-related lymphomas. We examined the EBV status of brain parenchymal B lymphocytes to investigate whether EBV-positive B lymphocytes are more frequent in HIV-infected brains than normal, thus explaining the propensity for CNS lymphomas in AIDS. In situ hybridization studies showed EBV positivity only in AIDS-related PCNSL cases within the lymphoma deposits. PCR-based studies detected high EBV copy numbers in PCNSL tumour tissue, and low copy numbers in AIDS cases with pleomorphic lymphoid infiltrates. As none of the B lymphocytes in this latter group were EBV positive on in situ hybridization, bearing in mind that this appears to be a prerequisite for PCNSL development, we find no evidence that pleomorphic infiltrates represent a pre-malignant PCNSL state.
authors.affiliation: Neuropathology Unit, University of Edinburgh, Alexander Donald Building, Western General Hospital, Edinburgh, UK.
authors.forename: I C
authors.initials: IC
authors.lastname: Anthony
authors.forename: D H
authors.initials: DH
authors.lastname: Crawford
authors.forename: J E
authors.initials: JE
authors.lastname: Bell
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology* / Q000473:pathology / Q000821:virology; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000276:immunology* / Q000821:virology; D001932:Brain Neoplasms / Q000276:immunology* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human; D006801:Humans; D017254:Leukemic Infiltration; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D016483:Lymphoma, AIDS-Related / Q000276:immunology* / Q000821:virology; D008297:Male; D017455:Receptors, IgE / Q000032:analysis
chemical_list: D015415:Biomarkers; D017455:Receptors, IgE