Science: revealing the mystery of HIV infection preventing the production of high affinity protective antibody

December 5, 2019 / Biovalley BIOON / - -- although there are abundant persistent antigens, chronic infections such as HIV infection usually do not induce protective antibody response Scientists have previously reported that memory B cells from patients with chronic HIV infection express transcription factor T-bet Almost all chronic human infections are related to the changes of memory B cell compartment, including CD19 overexpression and T-bet overexpression of memory B cells in the peripheral blood of HIV infected patients with chronic viremia Although these memory B cells are abundant, it is not clear how they are produced and whether they lead to the inefficiency of antibody mediated immune response in chronic infectious diseases In a new study, researchers from the National Institutes of Health (NIH), Yale University and the University of Maryland solved the problem by describing the B cells expressing T-bet in lymph nodes and identifying a strong T-bet feature in HIV specific memory B cells associated with adverse immune outcomes Relevant research results were published in the Journal of Science Translational Medicine on November 27, 2019 The title of the paper is "overexpression of T-bet in HIV infection is associated with acquisition of B cells outside general centers and poor affinity matching" Scanning electron micrograph of HIV infected T cells from NIAID Confocal microscopy and quantitative imaging showed that in the lymph nodes of HIV infected patients with chronic viremia, the B cells with high expression of t-beth were obviously aggregated outside the germinal center, which was crucial for the optimal antibody response The results of single cell analysis showed that the B cells with high expression of t-beth in the lymph nodes of HIV infected patients were only found in the memory B cells with high expression of CD19, and their expression of homing receptor in the germinal center decreased In addition, HIV-specific B cells in HIV infected patients accumulate and display unique transcriptome in the memory B cells with high expression of CD19 and t-beth in lymph nodes, which are similar to the memory B cells with high expression of CD19 and t-beth in blood and the germinal heart B cells in lymph nodes The memory B cells with high expression of CD19 and t-beth in lymph nodes are also related to the germinal center B cells in lymph nodes through the phylogenetic linkage based on B cell receptor (BCR), but they have lower BCR mutation frequency and decreased HIV neutralization ability, which is consistent with the reduction of affinity selection mediated by germinal center Therefore, in the case of chronic immune activation associated with HIV viremia, the inability of HIV specific B cells to enter or remain in the germinal center may help to explain the rarity of high affinity protective antibodies (bio Com) reference: James W Austin et al Overexpression of T-bet in HIV infection is associated with acquisition of B cells outside German centers and poor affinity matching Science Translational Medicine, 2019, DOI: 10.1126/scitranslmed.aax0904