Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.
Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (VH
) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without VH
-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques. FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeast and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive humans. Moreover, FDG precursors were predominately mutated IgM+
, thus suggesting that they originated from a pool of antigen-experienced IgM+
or marginal zone B cells.
Haynes, Barton Ford
Kelsoe, Garnett H.
Montefiori, David Charles
Moody, Michael Anthony
Perfect, John Robert
Saunders, Kevin O'Neil
Sempowski, Gregory David
Wiehe, Kevin J
Williams, Wilton Bryan
Williams, WB; Meyerhoff, RR; Edwards, RJ; Li, H; Manne, K; Nicely, NI; Henderson, R; Zhou, Y; Janowska, K; Mansouri, K; Gobeil, S; Evangelous, T; Hora, B; Berry, M; Abuahmad, AY; Sprenz, J; Deyton, M; Stalls, V; Kopp, M; Hsu, AL; Borgnia, MJ; Stewart-Jones, GBE; Lee, MS; Bronkema, N; Moody, MA; Wiehe, K; Bradley, T; Alam, SM; Parks, RJ; Foulger, A; Oguin, T; Sempowski, GD; Bonsignori, M; LaBranche, CC; Montefiori, DC; Seaman, M; Santra, S; Perfect, J; Francica, JR; Lynn, GM; Aussedat, B; Walkowicz, WE; Laga, R; Kelsoe, G; Saunders, KO; Fera, D; Kwong, PD; Seder, RA; Bartesaghi, A; Shaw, GM; Acharya, P; Haynes, BF
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