Research Report - Nikolaus-Fiebiger-Zentrum für Molekulare Medizin

Adoptive transfer of memory B cells as a new cell based therapy for infection
with Cytomegalovirus after transplantation
Florian Weisel, Martina Seefried, Anna Bootz*, Monika Dietz*, Astrid Karbach*, Julia
Winkler # , Andreas Mackensen # , Michael Mach*, Thomas Winkler, Technicians:
Andrea Schneider, Hannes Tittlbach
* Institute for Clinical and Molecular Virology
# Department of Internal Medicine 5, Hematology and Oncology
Severe disease associated with cytomegalovirus (CMV) infection is still a major
problem in transplant patients. Support of the patient’s immune defense against the
virus is therefore a major goal in transplantation medicine. We use the murine model
of CMV (MCMV) to investigate the potential of a cell-based strategy to support the
humoral antiviral immune response. We have previously shown that a transfer of
memory B cells was effective in protecting from an ongoing viral infection indicating a
therapeutic potential of virus specific memory B cells. In the recent period for this
report we analyzed the effector mechanisms for the protective effect of anti-CMV
antibodies. We have clear data that Fc-receptor (FcR) mediated mechanisms,
presumably antibody dependent cellular cytotoxicity (ADCC) play a major role in the
protective effect of antibodies in this viral disease. Determination of viral load in
organs (Fig. 1A, B) and analysis of survival (Fig. 1C) after serotherapy confirmed that
FcγR-deficient mice are not protected by administration of serum from MCMVimmune
donors. Further experiments with individual FcγRs revealed a complex and
partly redundant function of the different FcγRs. Whereas genetic deletion or antibody
blockade of either FcγRIII or FcγRIV alone have any measurable effect on antibody
protection, a combined defect of FcγRIII and FcγRIV had strong effects on protective
function of antibodies. With regard to effector cells we have the surprising finding that
NK cells, which are believed to be efficient effectors for ADCC, have surprisingly no
major role in antibody-mediated protection in CMV-infection as NK cell-depleted
animals were fully protected by serum therapy. Preliminary results indicate that
certain monocyte subpopulations that can be specifically depleted by clodronate
liposomes are important for antibody protection. We are currently studying the
function of these monocyte subpopulation and the role of FcγRI in antibody-mediated
protection in CMV-infection.
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