The role of Blimp-1 in the GC reaction: Differential expression of Blimp-1 upon immunization with TD and TI antigens

Abstract

Humoral responses against thymus-dependent (TD) antigens are characterized by Ig class switch, somatic hypermutations (SHM) and generation of memory. These processes are thought to occur in the specialized environment of the germinal center (GC). Some thymus-independent (TI) antigens, such as native dextran B512 (Dx) can also induce formation of GCs, but the responses do not undergo substantial affinity maturation or induction of memory. Immunization with TI Dx affects later TD responses against the same epitope, reducing Dx specific IgG1. We have studied if the different outcome of the TI- and TD-induced GC reaction is due to differences in plasma cell differentiation. The transcriptional repressor B lymphocyte-induced maturation protein, Blimp-1, was used as a marker for differentiation of plasma cells. We show that TI GCs contain Blimp-1 in early and mature GCs, in contrast to TD-induced GCs which strongly express Blimp-1 only in established GCs. Furthermore, the intensity of the Blimp-1 staining is stronger in TI GCs. In addition, we demonstrate that in TD responses after TI priming the pattern of Blimp-1 expression is a mixture of both TI and TD responses. This is novel evidence since these TD humoral responses against Dx display a TI isotype pattern.