Research ArticleHIV

Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation

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Science Translational Medicine  27 Nov 2019:
Vol. 11, Issue 520, eaax0904
DOI: 10.1126/scitranslmed.aax0904

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Abrogated antibody responses in chronic infection

Despite the presence of abundant and persistent antigen, chronic infections such as HIV often do not induce protective antibody responses. Memory B cells from people chronically infected with HIV have previously been reported to express the transcription factor T-bet. Austin et al. observed that T-bethi memory B cells were in the lymph nodes but not localized to germinal centers, where high-affinity antibody responses develop. Although clonally related to germinal center B cells, these T-bethi memory B cells had a lower frequency of somatic hypermutation and reduced capacity to neutralize HIV in vitro. Exclusion of T-bethi memory cells from germinal centers may be one mechanism contributing to the lack of a protective antibody response in most HIV infections.

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