Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes

Bancroft, Tara; DeBuysscher, Blair L.; Weidle, Connor; Schwartz, Allison; Wall, Abigail; Gray, Matthew D.; Feng, Junli; Steach, Holly R.; Fitzpatrick, Kristin S.; Gewe, Mesfin M.; Skog, Patrick D.; Doyle-Cooper, Colleen; Ota, Takayuki; Strong, Roland K.; Nemazee, David; Pancera, Marie; Stamatatos, Leonidas; McGuire, Andrew T.; Taylor, Justin J.

Nevertheless, the absence of CDRH3 sequences with high similarity to iglb12 led us to hypothesize that these sequences may be purged from the repertoire due to autoreactivity. Support for this hypothesis came from iglb12 staining of HEp-2 cells and experiments in which B cell deletion and anergy were observed in transgenic mice expressing the iglb12 heavy chain. These tolerance effects may explain why b12-like bNAbs have not been commonly identified from HIV-infected individuals in several studies. In contrast, bNAbs with other specificities are present and are identified in a large fraction of HIV-1 subjects who develop bNAb responses, such as those targeting the N332 supersite Landais et al., 2016; Rusert et al., 2016; Ditse et al., 2018) .