Antigen presentation and antigen-presenting cells in graft-versus-host disease - Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation - page 184

infused peritransplant to deplete host pDCs must be insufficient to deplete
pDCs infused with BM cells.

B cells

Activated B cells are unequivocally capable of activating T cells, including
naïve T cells [19,140] . Host B cells certainly present endogenous antigens on
MHCII and are capable of presenting exogenous antigens acquired by pino-
cytosis or by internalization of the B-cell receptor [141] . B cells have also
been suggested as the primary activators of autoreactive T cells in systemic
lupus erythematosus by virtue of the simultaneous engagement of their
antigen receptors and TLRs by nucleic acid-containing immune complexes
[19] . Therefore there would be a rationale for either host or donor B cells to
promote GVHD via alloreactive T-cell activation.

B cells have been a particularly intriguing potential target, as rituximab,
a humanized monoclonal antibody against human CD20 developed to
treat B-cell lymphomas, has been applied in the treatment of autoimmune
and inflammatory diseases with the goal of suppressing T-cell responses,
based on the demonstration in mouse models that B cells can promote
autoimmunity independent of autoantibody production [142,143] . The role
of B cells in GVHD is discussed in detail in Chapter 14, and here we focus on
data from mouse models.

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Schultz and colleagues [144] examined the role of recipient and donor B
cells in GVHD mediated by a mix of CD4 and CD8 cells by depleting B cells
in neonatal mice with anti- mu antibodies. Initial T-cell priming was reduced
in B-cell-depleted recipients; however, GVHD was not significantly different
in B-cell-replete and B-cell-depleted hosts. In these experiments donor cells
were also B-cell depleted and thus potential differences could not specifically
be ascribed to recipient B cells. By using hosts genetically deficient in mature
B cells, B cells were shown not to be required for GVHD initiation in experi-
mental models when GVHD is driven by full MHC mismatch [145] or miHA
mismatches [146] , in both CD4- and CD8-dependent models. In one report,
GVHD was exacerbated in B-cell-deficient hosts [145] , which was attributed
to an absence of IL-10-producing host B cells. Mice genetically deficient in
B cells have abnormal LN development due to the absence of lymphotoxin-
producing B cells. To address this, the impact of antibody-mediated host
B-cell depletion of WT mice was tested and did not result in reduced GVHD
[146] . Donor B cells or host B cells have been shown to be important in mod-
els of GVHD dominated by immune complex disease, not typical of human
GVHD. These studies are reviewed in detail elsewhere [147] .

Macrophages

Macrophages are a very diverse group of phagocytic cells derived from
monocyte precursors [9] . They are endowed with an array of antigen recep-
tors, can activate T cells, and also function as effector cells in anti-pathogen
responses. Beyond a role in inflammation, macrophages also participate in
wound healing and the resolution of inflammation. “What exactly is a mac-
rophage” is somewhat subjective, but in general they are distinguished from
dendritic cells (which are also diverse) by the absence of, or low expression
of, CD11c. Understanding the precise roles of macrophages in alloimmune