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, the B lymphocytes. During an immune response, the antibody genes in B cells are modified by programmed mutagenesis. This process takes place in the B cells that enter very special anatomical structures named germinal centers. Complex cell-cell interactions and fate decisions inside germinal centers allow the selection of those B cells in which the antibody genes gained mutations that increased the affinity of their antibody compared to other B cells.

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 locus of the antibody's heavy chain gene to swap exons that define the default IgM class (or isotype) for new ones that define 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 : 

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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