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Human Germinal Center B Cells Differ from Naïve and Memory B Cells in CD40 Expression and CD40L-Induced Signaling

Kanutte Huse1,2, Cara E Wogsland3, Hannah G Polikowsky3,4

  • 1Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

Cytometry. Part a : the Journal of the International Society for Analytical Cytology
|March 7, 2019
PubMed

Insights

Germinal center (GC) B cells show higher CD40 expression but lower NFκB signaling upon CD40 engagement compared to naive and memory B cells, revealing distinct cell-intrinsic responses in human GC reactions.

Area of Science:

  • Immunology
  • Cell Biology
  • Signaling pathways

Background:

  • CD40 signaling is crucial for germinal center (GC) formation and function in B cells.
  • The precise kinetics and magnitude of CD40 signaling during human GC reactions are not well understood.

Purpose of the Study:

  • To compare CD40 expression and signaling responses across different differentiation stages of mature human B cells.
  • To investigate cell-intrinsic differences in CD40-mediated signaling in naive, GC, and memory B cells.

Main Methods:

  • Utilized mass cytometry and phospho-specific flow cytometry to analyze protein expression and CD40L-induced signaling.
  • Employed viSNE and Marker Enrichment Modeling (MEM) for quantifying protein expression signatures in B cell subsets.

Main Results:

  • GC B cells exhibited higher CD40 protein expression than naive and memory B cells.
  • Despite higher CD40 expression, GC B cells showed reduced NFκB p65 phosphorylation within 30 minutes of CD40L activation.
  • GC B cells initially had higher IκBα levels, which were rapidly degraded to levels comparable to other B cell subsets post-activation.

Conclusions:

  • Human GC B cells possess distinct CD40 signaling characteristics compared to naive and memory B cells.
  • These cell-intrinsic differences in signaling contribute to the unique functions of B cells within the germinal center microenvironment.

Keywords:
CD40 signalinggerminal center B cellshuman tonsilsmass cytometryphospho-flow

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