T-independent type 2 antigens induce B cell proliferation in multiple splenic sites, but exponential growth is confined to extrafollicular foci.
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.
García de Vinuesa
C
C
Division of Immunity and Infection, University of Birmingham Medical School, GB.
O'Leary
P
P
Sze
D M
DM
Toellner
K M
KM
MacLennan
I C
IC
D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007075:Immunoglobulin M / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000276:immunology*
D000955:Antigens, T-Independent; D007074:Immunoglobulin G; D007075:Immunoglobulin M