The dynamics of the B follicle: understanding the normal counterpart of B-cell-derived malignancies

The repertoire of B cells secreting antibodies with unique antigen-binding specificities is produced at two stages: a primary B-cell repertoire is formed in the bone marrow through immunoglobulin gene rearrangements, whereas a secondary B-cell repertoire is generated in the peripheral lymphoid organs (spleen, lymph nodes and mucosa-associated lymphoid tissue) through somatic hypermutation and class-switch recombination upon antigen encounter. The latter events take place within highly specialized histological structures, designated B follicles, which are composed of distinct microanatomical compartments namely the follicle centre, lymphocytic corona and marginal zone. Each compartment comprises a particular subset of B cells, characterized by unique properties, thereby reflecting the complexity and variability in the spectrum of defence mechanisms against invading pathogens. The past years have spawned an avalanche of new data and information that encompasses both the structure and function of each compartment and its B cells. This review incorporates up-to-date information on peripheral B-cell differentiation into a challenging working model, thereby pointing to the structural and functional imprint of both the T-cell-dependent and T-cell-independent immune response on the B follicle. As such, this article aims to form an excellent base for a better understanding of the normal counterpart of B-cell-derived haematological malignancies (leukemias and lymphomas).