Correlation of anti-viral B cell responses and splenic morphology with expression of B cell-specific molecules.
This study attempted to evaluate and compare the role of various B cell-specific markers for anti-viral immune responses in mouse strains lacking molecules belonging to the B cell receptor (BCR) complex (IgM, Ig alpha and C(kappa)), the co-stimulatory molecules (CD19 and CD22), the protein kinases [Bruton's tyrosine kinase (Btk)] or the transcription factors (OBF-1). These mice were tested in two model infections [vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV)] using T cell-independent (TI) or T cell-dependent (TD) antigens. All mice controlled an LCMV infection indicating that cytotoxic T cell functions were within normal ranges. In contrast, OBF-1(-/-) mice were partially protected and mb-1(delta c/delta c) mice not at all protected against VSV infection, a virus that is controlled virtually exclusively by neutralizing antibodies. Susceptibility to VSV infection was correlated with structural defects in the spleen: absence of mature B cells and follicles with marginal zone macrophages and absence of germinal centers with follicular dendritic cells correlated with lack or substantial reduction of protective IgM and IgG responses respectively. The lack of kappa light chain did not affect the neutralizing response, indicating that it could easily be replaced by the lambda chain. Absence of the co-stimulatory molecules CD19 and CD22 or of the signaling molecule Btk had modulating effects, but did not increase susceptibility to VSV or LCMV. Our findings suggest that there are crucial molecules for B cell activation at the beginning (BCR complex) and the end (transcription) of the signaling cascade, whereas fine-tuning factors modulating the response in between exhibit considerable functional overlap.
Fehr
T
T
Institute of Experimental Immunology, Department of Pathology, University Hospital, Schmelzbergstrasse 12, 8091 Zürich, Switzerland.
López-Macías
C
C
Odermatt
B
B
Torres
R M
RM
Schubart
D B
DB
O'Keefe
T L
TL
Matthias
P
P
Hengartner
H
H
Zinkernagel
R M
RM
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D018941:Antigens, CD19 / Q000235:genetics; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D000956:Antigens, Viral / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology*; D051925:CD79 Antigens; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins / Q000235:genetics; D007114:Immunization; D007150:Immunohistochemistry; D037102:Lectins; D008216:Lymphocytic Choriomeningitis / Q000517:prevention & control*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011494:Protein Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D018353:Rhabdoviridae Infections / Q000517:prevention & control*; D051918:Sialic Acid Binding Ig-like Lectin 2; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
D000914:Antibodies, Viral; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D000956:Antigens, Viral; D051925:CD79 Antigens; C497868:Cd22 protein, mouse; C497882:Cd79a protein, mouse; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; C116351:SNAPC4 protein, human; D051918:Sialic Acid Binding Ig-like Lectin 2; D014157:Transcription Factors; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse