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A tolerogenic peptide down‐regulates mature B cells in bone marrow of lupus‐afflicted mice by inhibition of interleukin‐7, leading to apoptosis
Author(s) -
BenDavid Hava,
Sharabi Amir,
Parameswaran Reshmi,
Zinger Heidy,
Mozes Edna
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03109.x
Subject(s) - bone marrow , apoptosis , systemic lupus erythematosus , immunology , cancer research , medicine , biology , disease , biochemistry
Summary Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by T and B cells. It is characterized by a variety of autoantibodies and systemic clinical manifestations. A tolerogenic peptide, designated hCDR1, ameliorated the serological and clinical manifestations of SLE in both spontaneous and induced models of lupus. In the present study, we evaluated the status of mature B cells in the bone marrow (BM) of SLE‐afflicted mice, and determined the effect of treatment with the tolerogenic peptide hCDR1 on these cells. We demonstrate herein that mature B cells of the BM of SLE‐afflicted (New Zealand Black × New Zealand White)F 1 mice were largely expanded, and that treatment with hCDR1 down‐regulated this population. Moreover, treatment with hCDR1 inhibited the expression of the pathogenic cytokines [interferon‐γ and interleukin (IL)‐10], whereas it up‐regulated the expression of transforming growth factor‐β in the BM. Treatment with hCDR1 up‐regulated the rates of apoptosis of mature B cells. The latter was associated with inhibited expression of the survival Bcl‐xL gene and of IL‐7 by BM cells. Furthermore, the addition of recombinant IL‐7 abrogated the suppressive effects of hCDR1 on Bcl‐xL in the BM cells and resulted in elevated levels of apoptosis. Hence, the down‐regulated production of IL‐7 contributes to the hCDR1‐mediated apoptosis of mature B cells in the BM of SLE‐afflicted mice.