Henry Ford Health and Michigan State University Health Sciences has received a USD 2.86 million NIH R01 grant from the National Institute of Allergy and Infectious Diseases to investigate the molecular mechanisms governing immunoglobulin class switch recombination (CSR), a process central to adaptive immune function and implicated in B cell lymphoma development. The four-year award, running through May 2031, reflects sustained NIH interest in fundamental B cell biology with direct relevance to both vaccine science and oncology.
Imaging antibody diversification in live cells
CSR is the process by which B cells change the class of antibody they produce — switching, for example, from IgM to IgG or IgA — without altering antigen specificity. The switch is driven by activation-induced cytidine deaminase (AID), an enzyme that introduces DNA double-strand breaks at defined genomic switch regions. Because AID can also cause off-target mutations and chromosomal translocations, its activity is tightly regulated; dysregulation has been directly linked to B cell lymphoma formation.
A central unresolved question is how AID is selectively recruited to the immunoglobulin heavy chain locus rather than other genomic sites. The funded project will apply single-molecule live-cell imaging to visualize AID function and switch region transcription in real time, aiming to define recruitment specificity, CSR kinetics, and the role of transcription in directing DNA break induction.
Understanding the precision of AID targeting has implications beyond basic immunology. Aberrant CSR and AID activity are established drivers of B cell malignancies, including diffuse large B cell lymphoma and Burkitt lymphoma. Mechanistic clarity on how AID is constrained — or fails to be — could inform therapeutic strategies aimed at modulating genomic instability in B cell cancers, and may also yield insights relevant to optimizing antibody responses in vaccine contexts.