Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice.
CD20 mAb-mediated B cell depletion is an effective treatment for B cell malignancies and some autoimmune diseases. However, the full effects of B cell depletion on natural, primary, and secondary Ab responses and the maintenance of Ag-specific serum Ig levels are largely unknown. The relationship between memory B cells, long-lived plasma cells, and long-lived humoral immunity also remains controversial. To address the roles of B cell subsets in the longevity of humoral responses, mature B cells were depleted in mice using CD20 mAb. Peritoneal B cell depletion reduced natural and Ag-induced IgM responses. Otherwise, CD20+ B cell depletion prevented humoral immune responses and class switching and depleted existing and adoptively transferred B cell memory. Nonetheless, B cell depletion did not affect serum Ig levels, Ag-specific Ab titers, or bone marrow Ab-secreting plasma cell numbers. Coblockade of LFA-1 and VLA-4 adhesion molecules temporarily depleted long-lived plasma cells from the bone marrow. CD20+ B cell depletion plus LFA-1/VLA-4 mAb treatment significantly prolonged Ag-specific plasma cell depletion from the bone marrow, with a significant decrease in Ag-specific serum IgG. Collectively, these results support previous claims that bone marrow plasma cells are intrinsically long-lived. Furthermore, these studies now demonstrate that mature and memory B cells are not required for maintaining bone marrow plasma cell numbers, but are required for repopulation of plasma cell-deficient bone marrow. Thereby, depleting mature and memory B cells does not have a dramatic negative effect on preexisting Ab levels.
DiLillo
David J
DJ
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Hamaguchi
Yasuhito
Y
Ueda
Yoshihiro
Y
Yang
Kaiyong
K
Uchida
Junji
J
Haas
Karen M
KM
Kelsoe
Garnett
G
Tedder
Thomas F
TF
D000818:Animals; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D018951:Antigens, CD20 / Q000276:immunology*; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000628:therapy; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007167:Immunotherapy; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors; D008212:Lymphocyte Depletion; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000628:therapy; D051379:Mice; D008815:Mice, Inbred Strains; D010950:Plasma Cells / Q000187:drug effects* / Q000276:immunology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D007074:Immunoglobulin G; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1