A FORM OF IMMUNOLOGICAL-TOLERANCE THROUGH IMPAIRMENT OF GERMINAL CENTER DEVELOPMENT

Primary immunization with the T-cell-dependent antigen (4-hydroxy-3-ni trophenyl)acetyl (NP) coupled to human serum albumin results in the de velopment of two pathways of B-cell development, the extrafollicular p athway and the germinal center pathway. Soluble, deaggregated NP-human serum albumin injected before immunization results in a marked diminu tion of clonable higher-affinity antibody-forming cell precursors-i.e. , a form of immunologic tolerance within the secondary B-cell repertoi re. We describe here the cellular changes in the spleen that underlie this tolerance. Using multiparameter flow cytometry, we show that tole rant 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 almost-equal-to 2 x 10(5) such cells pe r spleen, whereas the tolerant mice have almost-equal-to 1 x 10(4) cel ls. Furthermore, we demonstrate by immunohistology a redction in the n umber of germinal centers containing lambda-bearing cells, characteris tic of the response of C57BL/6 mice to NP. Taken together, these data suggest an impairment of germinal center development in the tolerant m ice.