B-cell activation and lymphoma in patients with HIV.
The risk of developing non-Hodgkin lymphoma (AIDS lymphoma) is greatly increased in HIV infection. Disruption of immune function by HIV infection may contribute to lymphomagenesis by inducing (1) loss of immunoregulation of Epstein-Barr virus-infected B cells [immunoblastic and central nervous system (CNS) lymphoma] caused by loss of T-cell function, and (2) chronic B-cell hyperactivation enhancing the generation of genetic lesions (c- :immunoglobulin gene translocation, -6 overexpression) associated with some forms of AIDS lymphoma (Burkitt lymphoma-like small noncleaved cell lymphoma and large noncleaved cell lymphoma). Also, the overproduction of B-cell-stimulatory cytokines (interleukin 10 and 6) has the potential to contribute to tumor development by supporting the growth and viability of nascent lymphoma cell clones. Therefore, HIV infection-associated B-cell hyperactivation, including direct activation of B cells by various mechanisms, and chronic overproduction of B-cell-stimulatory cytokines have the potential to contribute to the development and growth of AIDS lymphoma. Several recent reports are discussed in this review, including recent work relevant to understanding the potential of a virus-encoded cytokine-like molecule, HHV8 vIL6, to induce B-cell hyperactivation in HIV-infected people, work pointing to the potential role of a chemokine (stromal cell-derived factor 1) in lymphomagenesis, and studies on phenotypic changes in circulating B cells in HIV infection.
Department of Microbiology, David Geffen School of Medicine, University of California-Los Angeles, 90095, USA. omartinez@mednet.ucla.edu
Otoniel
O
Martínez-Maza
Elizabeth Crabb
EC
Breen
D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D016867:Immunocompromised Host; D015850:Interleukin-6 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008223:Lymphoma / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D016483:Lymphoma, AIDS-Related / Q000276:immunology / Q000503:physiopathology; D010641:Phenotype; D014764:Viral Proteins / Q000494:pharmacology*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015850:Interleukin-6; D014764:Viral Proteins