Hardcoded B cell antigen recognition

Daniel Lingwood
Ragon Institute of Mass General, MIT and Harvard

Title: Hardcoded B cell antigen recognition

Daniel Lingwood is an Assistant Professor at the Ragon Institute of MGH, MIT and Harvard, and his many great papers are pushing frontier knowledge on antibody formation.

Lingwood has with his team identified natural gene-encoded pattern recognition motifs on human B cell receptors (BCRs), and shown that these can be triggered to re-center antibody output against ‘difficult-to-see’ vaccine targets. These have included functionally conserved broadly neutralizing antibody (bnAb) sites on hypervariable pathogens (e.g.  influenza virus, HIV, SARS-CoV-2 and gram-negative bacteria). Key to these discoveries were his engineering of transgenic mouse systems which recapitulate human antibody diversity and development. Immunization of these animals with germline-engaging vaccines succeeded in selectively expanding the corresponding gene-encoded human humoral response pathways, resulting in first in kind elicitation of high titer broadly protective serum antibodies.

Lingwood has further demonstrated that this humoral output can be controlled by subtle polymorphisms within the antibody gene sequence. Collectively, this work defines novel immunological solutions for rationally steering B cell and antibody development to broadly neutralize hypervariable pathogens that can ‘resist’ conventional vaccine approaches.
 

For more information, please visit the Ragon Institute web page about Lingwood's research.

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