Molecular biology of the B cell

We study the molecular mechanisms producing efficacious antibodies during the immune response. We also study how the malfunction of these mechanisms can cause immune pathologies or cancer.

Our research

Antibodies are proteins found in the serum that protect vertebrate animals, like humans, from infections and toxins. Antibodies are made by specialized cells named B lymphocytes. During an immune response, the antibody genes of B cells are modified by programmed mutagenesis. This process takes place in the B cells that enter anatomical structures named germinal centers. Complex interactions between immune cells inside germinal centers allow the selection of B cells with mutations in the immunoglobulin genes that happen to confer high affinity to their antibodies.

More in detail, the germinal center B cells modify the affinity of their antibody molecules by changing the sequence of the "variable" exon of the immunoglobulin genes by the mechanism of somatic hypermutation. Somatic hypermutation is initiated by Activation Induced Deaminase (AID), a unique enzyme that mutates DNA by transforming cytosine bases to uracils (a base normally found in RNA).

AID also triggers the mechanism of class switch recombination, which remodels the antibody heavy chain locus to change the default IgM class (or isotype) to IgG, IgE or IgA. Each antibody class has different biological properties, specialized to fight different threats.

Why does it matter?

The mechanisms regulating the activity of AID, somatic hypermutation, class switch recombination, and the germinal center function, are all necessary for efficient immune responses to infection and vaccines, as well as for the generation of immunological memory that confers long-term protection. Their dysfunction can result in immunodeficiency, autoimmunity, or B cell lymphoma.

Ongoing research projects :

    • Discovering and characterizing mechanisms regulating AID activity.

    • Studying mechanisms regulating germinal center B cell function.

    • Characterizing enzymes regulating the incorporation of uracil into the DNA.

Meet the PI:

Javier M Di Noia

JOIN US!

Motivated students that like research and you interested in pursuing MSc or PhD, please send us a letter of motivation, CV and university transcripts demonstrating academic performance. Graduate students can register at either Université de Montréal or McGill University.

Post-docs candidates should submit a letter of motivation, ideally with a brief project proposal, full CV (academic records, list of publications, technical skills) and names of 2 references including PhD supervisor.

Please email javier.di.noia(at)ircm.qc.ca

We are @ the IRCM (Institut de Recherches Cliniques de Montréal) in downtown Montreal. (Click find us)

110 Av des Pins Ouest H2W 1R7, Montréal, Québec, Canada

Contact Dr Javier M Di Noia

javier.di.noia(at)ircm.qc.ca

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