Antigen localization within the splenic marginal zone restores humoral immune response and IgG class switch in complement C4-deficient mice.


:Defects of early complement components (C1, C4 and C2) are associated with the development of systemic lupus erythematosus (SLE). The availability of complement knockout mice has increased our knowledge on the role of complement in the regulation of adaptive immunity. An impaired removal of apoptotic bodies, a disturbed clearance of IgG immune complexes (ICs) and an insufficient B-cell regulation via complement receptors CD21/CD35 have been discussed as explanations for the induction of autoimmunity; however, a unifying hypothesis for the loss of B-cell tolerance in the absence of C1 or C4 is still lacking. Using IgM-containing ICs, we observed a significant accumulation of antigen within the splenic marginal zone (MZ) of C4-deficient mice but not in C3-deficient or complement receptors CD21/CD35-deficient mice. The targeting of antigen toward the MZ restored adaptive immunity (antibody response and class switch) in C4-deficient animals. A new explanation for the association of SLE and complement C4 deficiency would be that in the absence of C4, natural antibodies (IgM type) localize more self-antigen toward the MZ so that the auto-antibody response is increased and autoimmune disease ensues. As such, an inadequate localization of self-antigens might be responsible for the annulment of peripheral B-cell tolerance in the absence of C4.


Int Immunol


International immunology


Zachrau B,Finke D,Kropf K,Gosink HJ,Kirchner H,Goerg S




Has Abstract


2004-12-01 00:00:00














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    abstract::Schnurri (Shn)-2 is a large zinc finger-containing protein, which plays a critical role in cell growth, signal transduction and lymphocyte development. In Shn-2-deficient (Shn-2(-/-)) CD4 T cells, the activation of nuclear factor-kappaB is up-regulated and their ability to differentiate into Th2 is enhanced. Here, we ...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Iwamura C,Kimura MY,Shinoda K,Endo Y,Hasegawa A,Yamashita M,Nakayama T

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  • Preferred CDRH3 lengths for antibodies with defined specificities.

    abstract::The third complementarity determining regions of heavy chain variable regions (CDRH3) confer the fine specificities of antibodies. The CDRH3 length distribution of all human or all mouse antibodies appears to be more or less random, with the human distribution having a wider spread. Since the Kabat database of aligned...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Johnson G,Wu TT

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  • IgE repertoire and immunological memory: compartmental regulation and antibody function.

    abstract::It is now generally recognized that bone marrow is the survival niche for antigen-specific plasma cells with long-term immunological memory. These cells release antibodies into the circulation, needed to prime effector cells in the secondary immune response. These antibodies participate in the surveillance for antigen...

    journal_title:International immunology

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    authors: Gould HJ,Wu YB

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  • MHC class II-mediated apoptosis of mature dendritic cells proceeds by activation of the protein kinase C-delta isoenzyme.

    abstract::The mature dendritic cell (DC) is considered to be the most potent antigen-presenting cell. Regulation of the DC, particularly its survival, is therefore critical. Mature DC are markedly more sensitive to HLA-DR-mediated apoptosis than immature DC. To further characterize this key survival difference, we compared the ...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Bertho N,Blancheteau VM,Setterblad N,Laupeze B,Lord JM,Drénou B,Amiot L,Charron DJ,Fauchet R,Mooney N

    更新日期:2002-08-01 00:00:00

  • Essential role of IL-7 receptor alpha in the formation of Peyer's patch anlage.

    abstract::We investigated the role of IL-7 receptor alpha (IL-7Ralpha) signal in the formation of Peyer's patch (PP) anlage. Although pan-lymphopenia is a common phenotype of rag2-/- and il7ralpha-/- mice, a close inspection revealed nodules corresponding to PP in the adult rag2-/- but not in the il7ralpha-/- mouse. In our prev...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Adachi S,Yoshida H,Honda K,Maki K,Saijo K,Ikuta K,Saito T,Nishikawa SI

    更新日期:1998-01-01 00:00:00

  • Reconstitution of the intermediate-affinity interleukin-2 receptor by cell fusion.

    abstract::Although IL-2 receptor beta chain (IL-2R beta) expressed in various lymphoid cell lines binds IL-2 with an intermediate affinity, IL-2R beta expressed in fibroblasts is unable to bind IL-2, suggesting that IL-2R beta is on its own not sufficient for generating the intermediate-affinity receptor and that lymphoid-speci...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Kuida K,Tanaka T,Kitamura F,Toyama-Sorimachi N,Miyasaka M

    更新日期:1992-10-01 00:00:00

  • Homing of lymphocytes into islets of Langerhans in prediabetic non-obese diabetic mice is not restricted to autoreactive T cells.

    abstract::Non-obese diabetic mice spontaneously develop a type 1 diabetes. The entry of leukocytes in the islets of Langerhans was studied in untreated and in irradiated mice. FITC-labeled cells from spleen, lymph nodes or bone marrow of healthy or diabetic donors did home to the inflamed islets of unmanipulated recipients. B a...

    journal_title:International immunology

    pub_type: 杂志文章


    authors: Faveeuw C,Gagnerault MC,Kraal G,Lepault F

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  • Role of co-stimulation in CD8+ T cell activation.

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Pardigon N,Bercovici N,Calbo S,Santos-Lima EC,Liblau R,Kourilsky P,Abastado JP

    更新日期:1998-05-01 00:00:00

  • Nuclear factor of activated T cells contributes to the function of the CD28 response region of the granulocyte macrophage-colony stimulating factor promoter.

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    journal_title:International immunology

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    authors: Shang C,Attema J,Cakouros D,Cockerill PN,Shannon MF

    更新日期:1999-12-01 00:00:00

  • Phenotype of B cells responding to the thymus-independent type-2 antigen polyvinyl pyrrolidinone.

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Whitmore AC,Haughton G,Arnold LW

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    authors: O'Hehir RE,Mach B,Berte C,Greenlaw R,Tiercy JM,Bal V,Lechler RI,Trowsdale J,Lamb JR

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    pub_type: 杂志文章


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    journal_title:International immunology

    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Lin H,Martelli MP,Bierer BE

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Yokota S,Minota S,Fujii N

    更新日期:2006-04-01 00:00:00

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Lake DF,Salgaller ML,van der Bruggen P,Bernstein RM,Marchalonis JJ

    更新日期:1999-05-01 00:00:00

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    journal_title:International immunology

    pub_type: 杂志文章


    authors: Adams K,Ackerly H,Cunningham K,Dunnick W

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    journal_title:International immunology

    pub_type: 杂志文章


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