B Cell Biology Andrea Cerutti, ICREA Research Professor

Mechanisms of Antibody Diversification and Memory Formation

A central theme of our research is the generation of antibody diversity and memory. In the bone marrow, immature B cells undergo V(D)J recombination, an antigen-independent process that generates their primary repertoire. Upon activation in peripheral lymphoid organs, these cells:

Class switch from IgM/IgD to IgG, IgA, or IgE.
Accumulate affinity-enhancing mutations through somatic hypermutation.
Differentiate into memory B cells and long-lived plasma cells.

These processes are regulated by activation-induced cytidine deaminase (AID) and typically involve the activation of follicular B cells by T follicular helper cells through a T cell-dependent (TD) pathway that promotes long-term protection and immune memory [Chen K et al.. Nature Rev. Immunol. 2020].

We also investigate a more rapid T cell-independent (TI) pathway involves innate-like splenic marginal zone B cells and maximizes immune protection by bridging virtually instantaneous innate immune responses by myeloid cells with slowly developing adaptive TD antibody responses by follicular B cells [Cerutti A. Nature Rev. Immunol. 2013]. Of note, TI and TD pathways are closely intertwined, the former involving granulocytes, [Puga I. et al., Nature Immunol. 2011; Chorny A. et al., J. Exp. Med. 2016], macrophages and dendritic cells [Grasset EK et al., Science Immunol. 2020] as well as innate lymphoid cells and stromal cells [Magri G. et al., Nature Immunol. 2014].