A form of immunologic tolerance through impairment of germinal center development.
Primary immunization with the T-cell-dependent antigen (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to human serum albumin results in the development of two pathways of B-cell development, the extrafollicular pathway and the germinal center pathway. Soluble, deaggregated NP-human serum albumin injected before immunization results in a marked diminution of clonable higher-affinity antibody-forming cell precursors--i.e., a form of immunologic tolerance within the secondary B-cell repertoire. We describe here the cellular changes in the spleen that underlie this tolerance. Using multiparameter flow cytometry, we show that tolerant mice develop far fewer NP-binding, peanut agglutinin-positive, or germinal center cells than the control immunized mice; 14 days after challenge control spleens have approximately 2 x 10(5) such cell per spleen, whereas the tolerant mice have approximately 1 x 10(4) cells. Furthermore, we demonstrate by immunohistology a reduction in the number of germinal centers containing lambda-bearing cells, characteristic of the response of C57BL/6 mice to NP. Taken together, these data suggest an impairment of germinal center development in the tolerant mice.
Pulendran
B
B
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Karvelas
M
M
Nossal
G J
GJ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology*; D037102:Lectins; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009596:Nitrophenols / Q000276:immunology; D019887:Peanut Agglutinin; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D013154:Spleen / Q000276:immunology*; D013997:Time Factors
D037102:Lectins; D009596:Nitrophenols; D019887:Peanut Agglutinin; D011947:Receptors, Antigen, B-Cell; C026654:4-hydroxy-3-nitrophenylacetyl-O-succinimide ester