4.8 Article

IκBNS expression in B cells is dispensable for IgG responses to T cell-dependent antigens

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.1000755

Keywords

nfkbid; NF-kappa B; conditional; CD79a; B cell responses; I kappa BNS

Categories

Funding

  1. Karolinska Institutet
  2. Swedish Research Council [2017-00968]
  3. Fondation Dormeur Vaduz
  4. Swedish Research Council [2017-00968] Funding Source: Swedish Research Council

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Mice lacking the I kappa BNS protein exhibit impaired antibody responses to both T cell-independent and T cell-dependent antigens. Conditional knock-out mice with I kappa BNS ablation specifically in B cells show normal T cell populations and germinal center formation, but still have defective antibody responses to T cell-dependent antigens.
Mice lacking the atypical inhibitory kappa B (I kappa B) protein, I kappa BNS, a regulator of the NF-kappa B pathway encoded by the nfkbid gene, display impaired antibody responses to both T cell-independent (TI) and T cell-dependent (TD) antigens. To better understand the basis of these defects, we crossed mice carrying floxed nfkbid alleles with mice expressing Cre under the transcriptional control of the Cd79a gene to create mice that lacked I kappa BNS expression only in B cells. Analyses of these conditional knock-out mice revealed intact CD4(+) and CD8(+) T cell populations, including preserved frequencies of FoxP3(+) regulatory T cells, which are known to be reduced in I kappa BNS knock-out mice. Like I kappa BNS knock-out mice, mice with conditional I kappa BNS ablation in B cells displayed defective IgM responses to TI antigens and a severe reduction in peritoneal B-1a cells. However, in contrast to mice lacking I kappa BNS altogether, the conditional I kappa BNS knock-out mice responded well to TD antigens compared to the control mice, with potent IgG responses following immunization with the viral antigen, rSFV-beta Gal or the widely used hapten-protein model antigen, NP-CGG. Furthermore, B cell intrinsic I kappa BNS expression was dispensable for germinal center (GC) formation and T follicular helper cell responses to NP-CGG immunization. The results presented here suggest that the defect in antibody responses to TD antigens observed in I kappa BNS knock-out mice results from a B cell extrinsic defect.

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