Expression of Toll-like receptors and costimulatory molecules in splenic B cells in a normal and abortion-prone murine pregnancy model

Am J Reprod Immunol. 2019 Aug;82(2):e13148. doi: 10.1111/aji.13148. Epub 2019 May 27.

Abstract

Problem: The regulatory role of B lymphocytes in the pregnancy-induced maternal immune response is not well recognized. B lymphocytes function as antigen-presenting cells (APCs) and regulate Toll-like receptors and costimulatory molecule expression in response to intrinsic and extrinsic signals. Therefore, the aim of this study was to determine the expression of TLR2, TLR4, TLR9, and MHC class II and the costimulatory molecules CD80, CD86, and CD40 in splenic B cells in a normal and abortion-prone murine pregnancy model.

Methods of study: The expression level of these molecules on female splenic B cells was investigated using real-time PCR and flow cytometry. The analysis was performed on the 3rd and 14th day of normal (CBA/JxBALB/c) and abortion-prone (CBA/JxDBA/2J) murine pregnancy.

Results: The expression of Tlr9, Cd86, and H2-Ab1 in splenic B cells on the 3rd day after mating was upregulated, whereas Tlr2 was downregulated in abortion-prone females. On day 14, we observed lower expression levels of Tlr4 and Cd80 and higher expression levels of Cd86 in CBA/J females mated with DBA/2J males. At the protein level, the differences were observed only on day 3 of pregnancy. TLR4 and CD40 molecules were upregulated in splenic B cells, while TLR9 and CD86 were downregulated in abortion-prone mice.

Conclusion: Differential expression of TLRs and costimulatory molecules in splenic B cells in abortion-prone and normal pregnancies suggests the involvement of these cells in the regulation of the immune response at the periphery in pregnant females.

Keywords: B cells; CD40; TLR4; abortion-prone; antigen-presenting cell; fetal tolerance; preimplantation pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous / immunology*
  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B7-1 Antigen / immunology*
  • B7-2 Antigen / immunology
  • CD40 Antigens / immunology
  • Female
  • Histocompatibility Antigens Class II / metabolism
  • Immune Tolerance
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Mice, Inbred DBA
  • Pregnancy
  • Spleen / immunology*
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / metabolism*
  • Toll-Like Receptor 9 / metabolism

Substances

  • B7-1 Antigen
  • B7-2 Antigen
  • CD40 Antigens
  • Cd86 protein, mouse
  • Histocompatibility Antigens Class II
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Tlr9 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptor 9