Differential response of IgM and IgG memory B cell populations to CD40L: insights of T cell - memory B cell interactions

Front Immunol. 2024 Jul 10:15:1432045. doi: 10.3389/fimmu.2024.1432045. eCollection 2024.

Abstract

Memory B cells (mBCs) are characterized by their long-term stability, fast reactivation, and capability to rapidly differentiate into antibody-secreting cells (ASCs). However, the role of T cells in the differentiation of mBCs, in contrast to naive B cells, remains to be delineated. We study the role of T cells in mBC responses, using CD40L stimulation and autologous T-B co-cultures. Our results showed that increased CD40L levels led to a selective increased proliferation of IgM+ mBC, which did not class-switched, resulting in higher frequencies of IgM+ ASCs and a lower frequency of IgG+ ASCs. The IgG+/IgA+ mBCs were unaffected. We further compared the transcription of immune-related genes in IgM+ and IgG+ pre-plasmablasts cultured at high (500 ng/mL) and low (50 ng/mL) CD40L levels. In response to increased CD40L levels, both populations exhibited a core response to genes related to activation (TRAF1, AKT3, CD69, and CD80). However, they differed in genes related to cytokine/chemokine/homing interactions (CCL3/4/17, LTA, NKX2-3, BCL2 and IL21R) and cell-cell interactions (HLADR, CD40, and ICOSL), which were largely confined to IgG+ cells. Our findings revealed that in co-cultures with a high T-ratio, the response was similar to that found in cultures with high CD40L levels. These results suggest that IgG+ mBCs have a greater capacity for proliferation and T cell interaction, and weaker migration capabilities, leading to a preference for an IgG response over IgM in the short term. This adaptable response could fine-tune the memory repertoire with different functions of IgG versus IgM mBCs.

Keywords: CD40L; T:B co-stimulation; memory B cell; plasma cell; plasmablast.

MeSH terms

  • CD40 Ligand* / immunology
  • CD40 Ligand* / metabolism
  • Cell Communication / immunology
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Humans
  • Immunoglobulin G* / immunology
  • Immunoglobulin M* / immunology
  • Immunoglobulin M* / metabolism
  • Immunologic Memory
  • Lymphocyte Activation / immunology
  • Memory B Cells* / immunology
  • Memory B Cells* / metabolism
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / metabolism

Substances

  • CD40 Ligand
  • Immunoglobulin M
  • Immunoglobulin G

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. ES laboratory was supported by the DFG grant SCHR 1658/1-1. ES is supported by the Else Kröner Fresenius Stiftung (EKFS). A-LS is supported by the Rahel-Hirsch-scholarship of Charité. HR-A was supported by the COLCIENCIAS scholarship call 727-2015. TD laboratory was supported by DFG grants (project Do491/10-1, 12-1, CRC/TR130, CRC Immunobone and CRC Because-Y/project 7). The DRFZ, a Leibniz Institute, was supported by the Senate of Berlin. We acknowledge support from the Open Access Publication Fund of the Charité Universitätsmedizin Berlin.