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 development except plasmacytes, lowers the threshold for B cell activation with anti-IgM by a factor of 100. The cytoplasmic tail of CD19 contains nine tyrosine residues as possible phosphorylation sites and is postulated to function as the signal transducing element for complement receptor (CR)2. Generation and analysis of CD19 gene-targeted mice revealed that T cell-dependent (TD) antibody responses to proteinaceous antigens were impaired, whereas those to T cell-independent (TI) type 2 antigens were normal or even augmented. These results are compatible with earlier complement depletion studies and the postulated function of CD19. To analyze the role of CD19 in antiviral antibody responses, 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 on antigen dose and replicative capacity than on antigen type. CR blocking experiments confirmed the role of CD19 as B cell signal transducer for complement. In contrast to immunization with protein antigens, infection of CD19(-/-) mice with replicating virus led to generation of specific germinal centers, which persisted for >100 d, whereas maintenance of memory antibody titers as well as circulating memory B cells was fully dependent on CD19. Thus, our study confirms a costimulatory role of CD19 on B cells under limiting antigen conditions and indicates an important role for B cell memory.
Fehr
T
T
Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland. thfehr@bluewin.ch
Rickert
R C
RC
Odermatt
B
B
Roes
J
J
Rajewsky
K
K
Hengartner
H
H
Zinkernagel
R M
RM
D000818:Animals; D000906:Antibodies / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology* / Q000502:physiology; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018858:Germinal Center / Q000378:metabolism*; D007114:Immunization; D007150:Immunohistochemistry; D007156:Immunologic Memory / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D017464:Receptors, Complement 3d / Q000276:immunology; D012209:Rhabdoviridae / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000906:Antibodies; D018941:Antigens, CD19; D000956:Antigens, Viral; D017464:Receptors, Complement 3d