Initial clonal expansion of germinal center B cells takes place at the perimeter of follicles.
Current models of the germinal center (GC) response propose that after stimulation at the edges of T cell zones, pre-GC B cells directly migrate to the center of follicles and proliferate to form GCs. We followed the interrelationship of proliferation, differentiation, and microenvironmental locale in populations of pre-GC B cells responding to antigen. In contrast to the predictions of current models, after accumulation at the T-B interface, these cells appeared at the perimeter of follicles adjacent to the marginal zone. There, they rapidly proliferated for several days but underwent no V gene hypermutation and little heavy-chain class switching. Their chemokine receptor expression pattern indicated that these cells were sessile, yet they had begun to acquire many phenotypic characteristics of GC B cells. The expanded clones were subsequently observed in the center of follicles, suggesting that GCs are created by coalescence of B cells from this follicular perimeter response.
Coffey
Francis
F
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Alabyev
Boris
B
Manser
Tim
T
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D020566:Dendritic Cells, Follicular / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic