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Blood, 1 May 2002, Vol. 99, No. 9, pp. 3319-3325
IMMUNOBIOLOGY
Human primary and memory cytotoxic T lymphocyte responses are
efficiently induced by means of CD40-activated B cells as
antigen-presenting cells: potential for clinical
application
Michael S. von Bergwelt-Baildon,
Robert H. Vonderheide,
Britta Maecker,
Naoto Hirano,
Karen S. Anderson,
Marcus O. Butler,
Zhinan Xia,
Wan Y. Zeng,
Kai W. Wucherpfennig,
Lee M. Nadler, and
Joachim L. Schultze
From the Department of Adult Oncology and the
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute;
Department of Medicine, Harvard Medical School; and the Department of
Medicine, Brigham and Women's Hospital, Boston, MA.
CD40 engagement is the major signal that induces B cells to
efficiently present antigen to T cells. We previously demonstrated that
human peripheral blood-derived CD40-activated B cells (CD40-B cells)
function as antigen-presenting cells (APCs). Here, we have established
a culture system to generate these APCs under clinically applicable
conditions using guanylic acid-grade soluble trimeric CD40
ligand. To monitor APC function and antigen loading for these cells,
simple and efficient quality control assays have been developed. Using
this approach, we demonstrate that CD40-B cells from healthy donors
and cancer patients are fully functional and equally expanded in
long-term cultures. These B cells boost robust memory T-cell responses,
but more importantly, they also prime naive T-cell responses against
neoantigens ex vivo. CD40-B cells overcome current obstacles,
such as the difficulty of isolation, generation, and long-term
expansion observed with other APCs. Therefore, they are an excellent
source of professional APCs for immune assessment, antigen
discovery, and antigen-specific immunotherapy.
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