Exploring lymphocyte differentiation pathways

Highlights in a 4-decade exploration of lymphocyte differentiation begin with comparative studies in birds and mammals leading to recognition of the separate T- and B-cell differentiation pathways and their cooperative interaction. The global effects of aborting IgM B-cell development with anti-mu antibodies indicated that B cells can undergo immunoglobulin isotype switching. A search for the mammalian bursa equivalent that began with an extended excursion through the gut-associated lymphoepithelial tissues ultimately led to the hematopoietic tissue origin of mammalian B cells. The identification of the precursors of B cells in hematopoietic tissues provided an expanded view of the life history of B cells. A recurring theme in this essay is the interplay between understanding normal lymphocyte differentiation and the defects that underlie immunodeficiency diseases and lymphoid malignancies.