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Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice.

Publication ,  Journal Article
DiLillo, DJ; Hamaguchi, Y; Ueda, Y; Yang, K; Uchida, J; Haas, KM; Kelsoe, G; Tedder, TF
Published in: J Immunol
January 1, 2008

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.

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Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

January 1, 2008

Volume

180

Issue

1

Start / End Page

361 / 371

Location

United States

Related Subject Headings

  • Plasma Cells
  • Mice, Inbred Strains
  • Mice
  • Lymphoma, B-Cell
  • Lymphocyte Function-Associated Antigen-1
  • Lymphocyte Depletion
  • Integrin alpha4beta1
  • Immunotherapy
  • Immunology
  • Immunologic Memory
 

Citation

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DiLillo, D. J., Hamaguchi, Y., Ueda, Y., Yang, K., Uchida, J., Haas, K. M., … Tedder, T. F. (2008). Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice. J Immunol, 180(1), 361–371. https://doi.org/10.4049/jimmunol.180.1.361
DiLillo, David J., Yasuhito Hamaguchi, Yoshihiro Ueda, Kaiyong Yang, Junji Uchida, Karen M. Haas, Garnett Kelsoe, and Thomas F. Tedder. “Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice.J Immunol 180, no. 1 (January 1, 2008): 361–71. https://doi.org/10.4049/jimmunol.180.1.361.
DiLillo DJ, Hamaguchi Y, Ueda Y, Yang K, Uchida J, Haas KM, et al. Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice. J Immunol. 2008 Jan 1;180(1):361–71.
DiLillo, David J., et al. “Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice.J Immunol, vol. 180, no. 1, Jan. 2008, pp. 361–71. Pubmed, doi:10.4049/jimmunol.180.1.361.
DiLillo DJ, Hamaguchi Y, Ueda Y, Yang K, Uchida J, Haas KM, Kelsoe G, Tedder TF. Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice. J Immunol. 2008 Jan 1;180(1):361–371.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

January 1, 2008

Volume

180

Issue

1

Start / End Page

361 / 371

Location

United States

Related Subject Headings

  • Plasma Cells
  • Mice, Inbred Strains
  • Mice
  • Lymphoma, B-Cell
  • Lymphocyte Function-Associated Antigen-1
  • Lymphocyte Depletion
  • Integrin alpha4beta1
  • Immunotherapy
  • Immunology
  • Immunologic Memory