An intrinsic propensity of murine peritoneal B1b cells to switch to IgA in presence of TGF-β and retinoic acid

PLoS One. 2013 Dec 6;8(12):e82121. doi: 10.1371/journal.pone.0082121. eCollection 2013.

Abstract

Aims: In the present study we have investigated the comparative switching propensity of murine peritoneal and splenic B cell subpopulations to IgA in presence of retinoic acid (RA) and TGF-β.

Methods and results: To study the influence of RA and TGF-β on switching of B cell subpopulations to IgA, peritoneal (B1a, B1b and B2 cells) and splenic (B1a, marginal zone, and B2) B cells from normal BALB/c mice were FACS purified, cultured for 4 days in presence of RA and TGF-β and the number of IgA producing cells was determined by ELISPOT assay or FACS analysis. In presence of TGF-β, peritoneal B1b cells switched to IgA more potently than other peritoneal B cell subpopulations. When TGF-β was combined with retinoic acid (RA), switching to IgA was even more pronounced. Under these conditions, "innate" B cells like peritoneal and splenic B1 cells and MZ B cells produced IgA more readily than B2 cells. Additionally, high frequency of nucleotide exchanges indicating somatic hypermutation in VH regions was observed. Besides IgA induction, RA treatment of sorted PEC and splenic B cells led to expression of gut homing molecules - α4β7 and CCR9. Intraperitoneal transfer of RA-treated B1 cells into Rag1(-/-) recipients resulted in IgA in serum and gut lavage, most efficiently amongst B1b cell recipients.

Conclusion: Present study demonstrates the differential and synergistic effect of RA and TGF-β on switching of different B cell subpopulations to IgA and establishes the prominence of peritoneal B1b cells in switching to IgA under the influence of these two factors. Our study extends our knowledge about the existing differences among B cell subpopulations with regards to IgA production and indicates towards their differential contribution to gut associated humoral immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Cell Line
  • Cell Movement / drug effects
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / metabolism
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin A / metabolism*
  • Immunoglobulin Class Switching / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Peritoneum / cytology*
  • Somatic Hypermutation, Immunoglobulin / drug effects
  • Spleen / cytology
  • Spleen / drug effects
  • Transforming Growth Factor beta / pharmacology*
  • Tretinoin / pharmacology*

Substances

  • Immunoglobulin A
  • Transforming Growth Factor beta
  • Tretinoin

Associated data

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Grant support

This work was supported in part by the German Research Council (DFG), the Ministry for Education and Research (BMBF) and the Helmholtz Association via the HZI Graduate School. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.