T-independent type 2 antigens induce B cell proliferation in multiple splenic sites, but exponential growth is confined to extrafollicular foci

Abstract

During the primary splenic response to the T-independent type 2 (TI-2) antigen (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll, small numbers of antigen-specific B cells have entered S phase of the cell cycle 24 h after intraperitoneal immunization. These are distributed in all splenic compartments (T zones, marginal zones, follicles, and red pulp), indicating early proliferation induced by NP-Ficoll does not require accessory signals delivered in a particular splenic microenvironment. Subsequently B blasts accumulate selectively in the outer T zone areas, but exponential growth leading to plasma cell production occurs only in extrafollicular foci. This growth peaks after 5 days, but 20% of peak numbers of antibody-containing cells are still present 3 months after immunization and 9% of these cells are proliferating. It is unclear if these late plasmablasts are sustained by self-renewal or continued recruitment of virgin cells into the response. Unlike TD and TI-1 responses NP-specific memory cells do not accumulate in the splenic marginal zones. The level of Cgamma3 switch transcripts increases during the first 24 h of the response, but does not increase further during exponential plasmablast growth.