Immunohistochemical characterization of splenic germinal centers in murine lupus

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  • MIURA KOJI
    Department of Pathology (II), Juntendo University School of Medicine Development & Medical Affairs Division, GlaxoSmithKline K. K.
  • XIU YAN
    Department of Pathology (II), Juntendo University School of Medicine
  • TSURUI HIROMICHI
    Department of Pathology (II), Juntendo University School of Medicine
  • TAKAHASHI KAZUKO
    Department of Pathology (II), Juntendo University School of Medicine
  • ZHANG DANQING
    Department of Pathology (II), Juntendo University School of Medicine
  • HIROSE SACHIKO
    Department of Pathology (II), Juntendo University School of Medicine

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Other Title
  • SLEマウスにおける脾臓リンパ濾胞胚中心の免疫組織化学的特徴
  • SLE マウス ニ オケル ヒゾウ リンパ ロホウハイチュウシン ノ メンエキ ソシキ カガクテキ トクチョウ

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Abstract

Objective : The germinal center (GC) provides a microenvironment within which affinity maturation of the humoral immune response and memory B cell formation takes place in response to T cell-dependent antigens. Follicular dendritic cells (FDCs) in GC play a role in antigen presentation by retaining immune complexes on their cell surface. Autoantibodies detected in systemic lupus erythematosus (SLE) show affinity maturation in a T cell-dependent fashion ; thus, GCs may play a critical role in the generation of pathogenic autoantibodies. In the present studies, we studied immunohistochemical characteristics of GCs in murine lupus. Methods : Immunohistochemical changes in splenic lymph follicles were examined in SLE-prone (NZB×NZW) F1 and BXSB mice using the three-color immunofluorescence technique. Results : GCs were spontaneously developed in SLE mice even before the onset of SLE, and the number and size of GCs increased with aging. Compared with GCs formed in KLH-immunized BALB / c mice, GCs in aged SLE mice with severe SLE contained larger numbers of T cells intermingled with activated B cells. While FDCs in KLH-immunized BALB / c mice expressed both CR1 and Fc γ RIIB molecules, aged SLE mice lacked Fc γ RIIB expression with aging. Conclusions : The present results of immunohistochemical studies on GCs of lupus mice were consistent with the idea that autoantibody production is highly T cell-dependent. The marked difference in expression levels of CR1 and Fc γ RIIB on FDCs in aged SLE mice may reflect the differential role of these two molecules for generation of high affinity autoantibodies. Further studies are needed to clarify the roles of CR1 and Fc γ RIIB on FDCs in tolerance breakdown and autoantibody production.

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