B cell hyperresponsiveness and expansion of mature follicular B cells but not of marginal zone B cells in NFATc2/c3 double-deficient mice.
Marginal zone (MZ) B cells and peritoneal B-1 cells provide a first defense system of thymus-independent Ab responses against foreign pathogens and therefore share a number of functional properties. Recently, development of B-1a cells was shown to be controlled by the transcription factor NFATc1. We show here that mice deficient for NFATc2 and c3 display a distinct lower representation of MZ B cells, which is correlated with a reduced capturing of trinitrophenyl-Ficoll. In contrast, mature follicular B cells from NFATc2/c3-/- mice are strongly increased in number. NFATc2/c3-/- B cells exhibit a marked increase in BCR-induced intracellular Ca2+ mobilization and proliferation. However, trinitrophenyl-Ficoll-specific IgM and IgG3 responses of NFATc2/c3-deficient mice are intact, and chimeric mice reconstituted with NFATc2/3-deficient B cells show a normal number of MZ B cells and normal BCR responses. These observations suggest that the strongly elevated Th2 cytokine milieu in NFATc2/c3-deficient mice leads to a hyperactivation of mature, follicular B cells, whereas MZ B cells are less responsive to these signals.
Samanta
Devapriya Nandini
DN
Department of Molecular Pathology, Institute of Pathology, University of Würzburg, Würzburg, Germany.
Palmetshofer
Alois
A
Marinkovic
Dragan
D
Wirth
Thomas
T
Serfling
Edgar
E
Nitschke
Lars
L
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D020013:Calcium Signaling; D002454:Cell Differentiation; D002678:Chimera / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D005362:Ficoll / Q000031:analogs & derivatives* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics; D014301:Trinitrobenzenes / Q000276:immunology
D016207:Cytokines; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C494007:Nfatc2 protein, mouse; D009687:Nuclear Proteins; D011947:Receptors, Antigen, B-Cell; C020529:TNP-ficoll; D014157:Transcription Factors; D014301:Trinitrobenzenes; D005362:Ficoll