Pathophysiological aspects of memory B-cell development

B cells follow two functionally distinct pathways of development: a classical germinal center (GC) T-dependent pathway in which diversification and maturation generate a slow, but virtually unlimited high-affinity response to cognate antigens; and a marginal zone (MZ) T-independent pathway providing a first line of ‘innate-like’ defense against specific pathogens. Cells populating these two distinct locations are the normal counterparts of two clinically important pathological entities, follicular lymphoma (FL) and MZ lymphoma (MZL). FL and MZ represent paradigms of two rising concepts of lymphomagenesis, protracted preclinical and antigen-driven lymphoproliferation, respectively. Integrating the mechanisms and functions of MZ and GC B cells and the distinctive features of their pathological counterparts should provide essential clues to the understanding of their malignant development, and should offer new insights into the design of effective treatments for B-cell lymphomas.