ANTIVIRAL PROTECTION AND GERMINAL CENTER FORMATION, BUT IMPAIRED B-CELL MEMORY IN THE ABSENCE OF CD19

Coligation of CD19, a molecule expressed during all stages of B cell d evelopment except plasmacytes, lowers the threshold for B cell activat ion with anti-IgM by a factor of 100. The cytoplasmic tail of CD19 con tains nine tyrosine residues as possible phosphorylation sites and is postulated to function as the signal transducing element for complemen t receptor (CR)2. Generation and analysis oi CD19 gene-targeted mice r evealed that T cell-dependent (TD) antibody responses to proteinaceous antigens were impair-ed, whereas those to T cell-independent (TI) typ e 2 antigens were normal or even augmented. These results are compatib le with earlier complement depletion studies and the postulated functi on of CD19. To analyze the role of CD19 in antiviral antibody response s, we immunized CD19(-/-) mice with viral antigens of TI-1, TI-2, and TD type. The effect of CD19 on TI responses was more dependent oil ant igen dose and replicative capacity than on antigen type. CR blocking e xperiments confirmed the role of CD19 as B cell signal transducer for complement. In contrast to immunization with protein antigens, infecti on of CD19(-/-) mice with replicating virus led to generation of speci fic germinal centers, which persisted for >100 d, whereas maintenance of memory antibody titers as well as circulating memory B cells was fu lly dependent on CD19. Thus, our study confirms a costimulatory role o f CD19 on B cells under limiting antigen conditions and indicates an i mportant role for B cell memory.