The peritoneal cavity provides a protective niche for B1 and conventional B lymphocytes during anti-CD20 immunotherapy in mice.
Although anti-CD20 immunotherapy effectively treats human lymphoma and autoimmune disease, the in vivo effect of immunotherapy on tissue B cells and their subsets is generally unknown. To address this, anti-mouse CD20 mAbs were used in a mouse model in which the extent and kinetics of tissue B cell depletion could be assessed in vivo. CD20 mAb treatment depleted most mature B cells within 2 days, with 95-98% of B cells in the bone marrow, blood, spleen, lymph nodes, and gut-associated lymphoid tissues depleted by day 7, including marginal zone and follicular B cells. The few spleen B cells remaining after CD20 mAb treatment included pre-B, immature, transitional, and some B1 B cells that expressed CD20 at low levels. By contrast, peritoneal cavity B cells expressed normal CD20 densities and were coated with CD20 mAb, but only 30-43% of B1 cells and 43-78% of B2 cells were depleted by day 7. Spleen B cells adoptively transferred into the peritoneal cavity were similarly resistant to mAb-induced depletion, while transferred B cells that had migrated to the spleen were depleted. However, peritoneal B1 and B2 cells were effectively depleted in mAb-treated wild-type and C3-deficient mice by thioglycolate-induced monocyte migration into this otherwise privileged niche. Inflammation-elicited effector cells did not promote peritoneal cavity B cell depletion in FcR-deficient mice treated with CD20 mAb. Thus, the majority of CD20(+) cells and B cell subsets within lymphoid tissues and the peritoneum could be depleted efficiently in vivo through Fc-dependent, but C-independent pathways during anti-CD20 immunotherapy.
Hamaguchi
Yasuhito
Y
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Uchida
Junji
J
Cain
Derek W
DW
Venturi
Guglielmo M
GM
Poe
Jonathan C
JC
Haas
Karen M
KM
Tedder
Thomas F
TF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D018951:Antigens, CD20 / Q000032:analysis / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects*; D003176:Complement C3; D007167:Immunotherapy / Q000009:adverse effects*; D007700:Kinetics; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D010529:Peritoneal Cavity / Q000166:cytology / Q000502:physiology*; D011961:Receptors, Fc
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D003176:Complement C3; D011961:Receptors, Fc