RP105-lacking B cells from lupus patients are responsible for the production of immunoglobulins and autoantibodies

Yuji Kikuchi, Syuichi Koarada, Yoshifumi Tada, Osamu Ushiyama, Fumitaka Morito, Noriaki Suzuki, Akihide Ohta, Kensuke Miyake, Masao Kimoto, Takahiko Horiuchi, Kohei Nagasawa

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Abstract

Objective. We previously reported that B cells lacking the RP105 molecule, which proved to be highly activated B cells, are increased in the peripheral blood of patients with systemic lupus erythematosus (SLE). In the present study, we attempted to determine whether RP105-negative B cells obtained from SLE patients would be capable of producing autoantibodies as well as immunoglobulins. Methods. RP105-positive and RP105-negative B cells, sorted by cell sorter, were cultured for 5 days without stimulation, or were stimulated with Staphylococcus aureus Cowan 1 strain (SAC) or recombinant interleukin-6 (IL-6). For the assay of autoantibodies, RP105-positive and R-P105-negative B cells were cultured separately for 10 days with anti-CD3 antibody- stimulated T cells. The production of immunoglobulins and autoantibodies was determined by enzyme-linked immunosorbent assay. Results. We demonstrated that RP105-negative B cells, but not RP105-positive B cells, obtained from SLE patients could spontaneously produce IgG and IgM in vitro until day 5. SAC and IL-6 enhanced production of IgG and IgM by RP105-negative B cells but failed to induce such production by RP105-positive B cells. The latter cells, however, when cocultured with activated T cells in the presence of IL-10, produced IgG, although the amount was very small compared with that produced by RP105-negative B cells. Most important, under these conditions, anti-double-stranded DNA antibodies were produced only by the RP105-negative B cells obtained from SLE patients. Conclusion. These data indicate that RP105-negative B cells, constituting a subset of B cells in SLE patients, are highly activated and may be responsible for the production of autoantibodies as well as polyclonal immunoglobulins.

Original languageEnglish
Pages (from-to)3259-3265
Number of pages7
JournalArthritis and rheumatism
Volume46
Issue number12
DOIs
Publication statusPublished - Dec 1 2002

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Autoantibodies
Immunoglobulins
B-Lymphocytes
Systemic Lupus Erythematosus
Immunoglobulin G
Immunoglobulin M
Staphylococcus aureus
Interleukin-6
B-Lymphocyte Subsets
T-Lymphocytes
Interleukin-10
Anti-Idiotypic Antibodies
Enzyme-Linked Immunosorbent Assay
Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Kikuchi, Y., Koarada, S., Tada, Y., Ushiyama, O., Morito, F., Suzuki, N., ... Nagasawa, K. (2002). RP105-lacking B cells from lupus patients are responsible for the production of immunoglobulins and autoantibodies. Arthritis and rheumatism, 46(12), 3259-3265. https://doi.org/10.1002/art.10672

RP105-lacking B cells from lupus patients are responsible for the production of immunoglobulins and autoantibodies. / Kikuchi, Yuji; Koarada, Syuichi; Tada, Yoshifumi; Ushiyama, Osamu; Morito, Fumitaka; Suzuki, Noriaki; Ohta, Akihide; Miyake, Kensuke; Kimoto, Masao; Horiuchi, Takahiko; Nagasawa, Kohei.

In: Arthritis and rheumatism, Vol. 46, No. 12, 01.12.2002, p. 3259-3265.

Research output: Contribution to journalArticle

Kikuchi, Y, Koarada, S, Tada, Y, Ushiyama, O, Morito, F, Suzuki, N, Ohta, A, Miyake, K, Kimoto, M, Horiuchi, T & Nagasawa, K 2002, 'RP105-lacking B cells from lupus patients are responsible for the production of immunoglobulins and autoantibodies', Arthritis and rheumatism, vol. 46, no. 12, pp. 3259-3265. https://doi.org/10.1002/art.10672
Kikuchi, Yuji ; Koarada, Syuichi ; Tada, Yoshifumi ; Ushiyama, Osamu ; Morito, Fumitaka ; Suzuki, Noriaki ; Ohta, Akihide ; Miyake, Kensuke ; Kimoto, Masao ; Horiuchi, Takahiko ; Nagasawa, Kohei. / RP105-lacking B cells from lupus patients are responsible for the production of immunoglobulins and autoantibodies. In: Arthritis and rheumatism. 2002 ; Vol. 46, No. 12. pp. 3259-3265.
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AU - Morito, Fumitaka

AU - Suzuki, Noriaki

AU - Ohta, Akihide

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AU - Horiuchi, Takahiko

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AB - Objective. We previously reported that B cells lacking the RP105 molecule, which proved to be highly activated B cells, are increased in the peripheral blood of patients with systemic lupus erythematosus (SLE). In the present study, we attempted to determine whether RP105-negative B cells obtained from SLE patients would be capable of producing autoantibodies as well as immunoglobulins. Methods. RP105-positive and RP105-negative B cells, sorted by cell sorter, were cultured for 5 days without stimulation, or were stimulated with Staphylococcus aureus Cowan 1 strain (SAC) or recombinant interleukin-6 (IL-6). For the assay of autoantibodies, RP105-positive and R-P105-negative B cells were cultured separately for 10 days with anti-CD3 antibody- stimulated T cells. The production of immunoglobulins and autoantibodies was determined by enzyme-linked immunosorbent assay. Results. We demonstrated that RP105-negative B cells, but not RP105-positive B cells, obtained from SLE patients could spontaneously produce IgG and IgM in vitro until day 5. SAC and IL-6 enhanced production of IgG and IgM by RP105-negative B cells but failed to induce such production by RP105-positive B cells. The latter cells, however, when cocultured with activated T cells in the presence of IL-10, produced IgG, although the amount was very small compared with that produced by RP105-negative B cells. Most important, under these conditions, anti-double-stranded DNA antibodies were produced only by the RP105-negative B cells obtained from SLE patients. Conclusion. These data indicate that RP105-negative B cells, constituting a subset of B cells in SLE patients, are highly activated and may be responsible for the production of autoantibodies as well as polyclonal immunoglobulins.

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