Spatial model of affinity maturation in germinal centers

Abstract

Affinity maturation of humoral responses to T-cell-dependent antigens occurs in germinal centers (GC). In GCs antigen-specific B cells undergo rounds of somatic mutations that alter their affinity. High-affinity mutants take over GCs very soon after they appear; the replacement rate is as high as 4 per day (Radmacher et al., Immunol. Cell Biol. 76 (1998) 373). To gain more insight into this selection process, we present a spatial model of GC reactions, where B cells compete for survival signals from follicular dendritic cells (FDC). Assuming that high-affinity B cells have increased cellular adhesion to FDCs, we obtain an affinity-based sorting of B cells on the FDC. This sorting imposes a very strong selection and therefore results in a winner-takes-all behavior. By comparing our sorting model with ‘‘affinity-proportional selection models’’, we show that this winner-takes-all selection is in fact required to account for the fast rates at which high affinity mutants take over GCs. Another important feature of in vivo GC reactions is that they are non-mixed, i.e. GCs contain either no high-affinity cells at all or they are dominated by high-affinity cells. We here show that this all-or-none behavior can be obtained if B cells are sorted based on their affinity on the FDC surface. Affinity-proportional selection models, in contrast, always produce mixed GCs. r 2003 Elsevier Science Ltd. All rights reserved.