The B cell memory program: cell fate determinants and functional diversity of B cell subsets

Objective

B cells are responsible for the humoral arm of the immune response and most successful
vaccines in humans are antibody-based. Depending on the pathogen, specific B cell subsets are
mobilized and a variety of innate, intermediate or adaptive responses are produced. In some
cases these responses generate memory in anticipation of a re-encounter with the same pathogen.
B cells can also present antigens to T cells, and enhance or suppress immune responses,
depending in which T cell context they are primed.
The present project aims to describe new innate-like and memory B cell subsets and to
unravel the molecular switch allowing the differentiation and the long-term maintenance
into the memory program. This will be done by combining approaches in both humans and
mice, in order to reveal the analogies and the differences between these two immune
systems.
Our main specific aims are 1) to establish a reporter cell line that, by complementation with a
cDNA library from human centrocytes and memory B cells, should allow the identification of a
master gene able to trigger the memory program 2) to compare various antigenic and
endogenous stimuli in terms of formation of various innate-like and memory subsets, using a
mouse model that, by marking irreversibly B cells during an immune response, has allowed us to
reveal new layers of B-cell memory 3) to study the endogenous and exogenous signals that
support the development of marginal zone B cells in humans 4) to unravel the genes that govern
long-term B cell memory, by isolating anti-vaccinia virus long-lived human memory B cells. The
general ambition is to provide new insights into the complexity of the B cell compartment that
should allow the improvement of B-cell targeted vaccination strategies.

Fields of science

Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

EU contribution

€ 1 695 980,00

Address

RUE DE TOLBIAC 101
75654 Paris
France

Region

Ile-de-France Ile-de-France Paris

Activity type

Research Organisations

Administrative Contact

Nicolas Jeanjean (Mr.)

Principal investigator

Jean-Claude Weill (Prof.)

Links

Contact the organisation Website

Total cost

No data

Beneficiaries (1)