Targeting Antigens to CD180 but Not CD40 Programs Immature and Mature B Cell Subsets to Become Efficient APCs

J Immunol. 2019 Oct 1;203(7):1715-1729. doi: 10.4049/jimmunol.1900549. Epub 2019 Sep 4.


Targeting Ags to the CD180 receptor activates both B cells and dendritic cells (DCs) to become potent APCs. After inoculating mice with Ag conjugated to an anti-CD180 Ab, B cell receptors were rapidly internalized. Remarkably, all B cell subsets, including even transitional 1 B cells, were programed to process, present Ag, and stimulate Ag-specific CD4+ T cells. Within 24-48 hours, Ag-specific B cells were detectable at T-B borders in the spleen; there, they proliferated in a T cell-dependent manner and induced the maturation of T follicular helper (TFH) cells. Remarkably, immature B cells were sufficient for the maturation of TFH cells after CD180 targeting: TFH cells were induced in BAFFR-/- mice (with only transitional 1 B cells) and not in μMT mice (lacking all B cells) following CD180 targeting. Unlike CD180 targeting, CD40 targeting only induced DCs but not B cells to become APCs and thus failed to efficiently induce TFH cell maturation, resulting in slower and lower-affinity IgG Ab responses. CD180 targeting induces a unique program in Ag-specific B cells and to our knowledge, is a novel strategy to induce Ag presentation in both DCs and B cells, especially immature B cells and thus has the potential to produce a broad range of Ab specificities. This study highlights the ability of immature B cells to present Ag to and induce the maturation of cognate TFH cells, providing insights toward vaccination of mature B cell-deficient individuals and implications in treating autoimmune disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology*
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • B-Cell Activation Factor Receptor / genetics
  • B-Cell Activation Factor Receptor / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • CD40 Antigens / genetics
  • CD40 Antigens / immunology*
  • Mice
  • Mice, Knockout
  • Rats
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology


  • Antigens, CD
  • B-Cell Activation Factor Receptor
  • CD40 Antigens
  • Ly78 protein, mouse
  • Tnfrsf13c protein, mouse