Previous animal model studies have found that broadly neutralising antibodies (bNAbs) against HIV-1 that are isolated from infected patients are protective. HIV-1 envelope glycoprotein (Env) is the only viral target of bnAbs but it can also be targeted by binding, non-neutralising antibodies. So far, Env-based immunogens tested in various animal models and in humans have elicited binding and autologous neutralising antibodies but mostly not bNAbs. The authors were interested in the underlying reasons for this and the binding specificities of the elicited antibodies, which have been examined through serologic methods and monoclonal antibody isolation. However, such approaches provide limited information on the ontogenies and clonal B cell lineages that expand following Env-immunisation. Therefore the authors used both serological analysis plus high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterisation methods, to compare the B cell and antibody responses produced in non-human primates by two forms of the HIV clade C Env 426c. One included the full length extracellular portion of Env, while the other lacked the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites. The authors found that the two forms were equally immunogenic, but only the latter elicited neutralising antibodies and it did this by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003–0.02%) of total B cells. Therefore it appears that Env antigenic differences do drastically affect the expansion of particular B cell lineages and therefore immunogen-design efforts need to stimulate the expansion of cells expressing particular B cell receptors.
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