Germinal centers without T cells.
Germinal centers are critical for affinity maturation of antibody (Ab) responses. This process allows the production of high-efficiency neutralizing Ab that protects against virus infection and bacterial exotoxins. In germinal centers, responding B cells selectively mutate the genes that encode their receptors for antigen. This process can change Ab affinity and specificity. The mutated cells that produce high-affinity Ab are selected to become Ab-forming or memory B cells, whereas cells that have lost affinity or acquired autoreactivity are eliminated. Normally, T cells are critical for germinal center formation and subsequent B cell selection. Both processes involve engagement of CD40 on B cells by T cells. This report describes how high-affinity B cells can be induced to form large germinal centers in response to (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll in the absence of T cells or signaling through CD40 or CD28. This requires extensive cross-linking of the B cell receptors, and a frequency of antigen-specific B cells of at least 1 in 1,000. These germinal centers abort dramatically at the time when mutated high-affinity B cells are normally selected by T cells. Thus, there is a fail-safe mechanism against autoreactivity, even in the event of thymus-independent germinal center formation.
de Vinuesa
C G
CG
Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Cook
M C
MC
Ball
J
J
Drew
M
M
Sunners
Y
Y
Cascalho
M
M
Wabl
M
M
Klaus
G G
GG
MacLennan
I C
IC
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000032:analysis; D005362:Ficoll; D018858:Germinal Center / Q000502:physiology*; D006241:Haptens; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009596:Nitrophenols; D019887:Peanut Agglutinin; D010648:Phenylacetates; D015398:Signal Transduction; D013154:Spleen / Q000187:drug effects; D013601:T-Lymphocytes / Q000502:physiology*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D006241:Haptens; D008562:Membrane Glycoproteins; D009596:Nitrophenols; D019887:Peanut Agglutinin; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid; D005362:Ficoll