TGF-$\beta$3 Selectively Induces Mouse IgA and IgG2b isotype

TGF-$\beta$3는 마우스 IgA, IgG2b 항체의 선택적 유도작용

  • 이은경 (강원대 자연대학 미생물학과) ;
  • 박석래 (강원대 자연대학 미생물학과) ;
  • 전계택 (강원대 자연대학 미생물학과) ;
  • 김평현 (강원대 자연대학 미생물학과) ;
  • 이세원 (강원대 자연대학 미생물학과) ;
  • 최의열 (한림대 자연대학 생명과학부)
  • Published : 1999.06.01

Abstract

TGF-$\beta$3 is among five TGF-$\beta$ isolorms and shows 80% sequence identity to TGF-$\beta$I, a prototype of TGF--$\beta$. It has been reported that TGF-$\beta$I, particularly in the presence of IL-2 or L-5, increases the pmduction of IgA and IgG2b isoiypes by LPS-actwated murine B cells. We examined the effect of TGF-P3 on Ig synlhesis by B cells from different lymphoid origins. IgA induction by TGP-$\beta$3 was mardnal in LPS-activated spleen B cell culture, while 1gA production was markedly enhanced in the culture shulated with TGF-$\beta$P3 and L-5. In addition, number of IgA secreting cells was increased by TGF-$\beta$P3. Under the same conditions, TGP-$\beta$3 alone was enough to increase IgG2b production but IgM and 1gGl. Sirmlar patiem of IgA and IgGZb enbancement by TGF-$\beta$3 and L-5 was observed in the cullures of mesenteric lymph node B cells. Thus, overall effect of TGF-$\beta$3 on Ig synthesis was quite similar to that of TGF-$\beta$I. Nonetheless, it remains to be underslood whether TGF-$\beta$3 is an important modulator in B cell differentiation since regulation of TGF-$\beta$3 expression is considered to differ from that of TGF-$\beta$I

TGF-$\beta$1은 LPS 로 자극시킨 마우스의 spleen B cell 의 IgA와 IgG2b의 항체 합성을 선택적으로 증가시킨다고 알려져있다. 본 연구에서는 TGF-$\beta$1과 80%의 아미노산을 공유하는 TGF-$\beta$3가 마우스 spleen B cell 과 mesenteric lymph node B cell의 항체 합성에 미치는 영향을 IL-5와 함께 조사하였다. LPS로 활성화된 spleen B cell 에 TGF-$\beta$3만을 처리한 조건에서 IgA 항체합성이 약간 증가하였고, IL-5와 함께 넣어 준 배양조건에서는 IgA 항체가 현격히 증가하였다 IgG2b 합성의 증가는 TGF-$\beta$3 자극만으로도 가능하였고 IgA 와는 달리 IL-5 의 첨가 효과는 관찰되지 않았다. 한편, TGF-$\beta$3는 IgM 과 IgG1 항체 합성을 감소시켰고, IL-5와 함께 존재한 경우에도 의미있는 합성 증가는 볼 수 없었다. ELISPOT assay로 IgA 합성 세포수의 변화를 조사해본 결과, TGF-$\beta$3 단독으로도 IgA 합성세포수를 증가시켰으며, 이때 IL-5가 존재하였을 때 세포수가 조금 더 증가하였다. 이상의 결과는 TGF-$\beta$3가 약간의 차이는 있지만 TGF-$\beta$1과 유사하게 항체합성 패턴에 영향을 미침을 보여준다. 마지막으로, TGF-$\beta$3과 IL-5에 대한 MLN B cell 의 IgA와 IgG2b 항체합성 패턴은 spleen B cell 과 비슷하였다. 그러나 MLN B cell 의 IgG1 항체 합성은 spleen B cell과는 달리 TGF-$\beta$3에 의해 증가하였다. 본 실험의 결과는 전반적으로 TGF-$\beta$3가 TGF-$\beta$1과 비슷한 정도로 마우스 B cell의 항체합성에 영향을 미침을 보여준다. 그렇지만, 생체 내에서TGF-$\beta$3의 발현조절이 TGF-$\beta$1과 다를 것으로 예상됨으로 과연 TGF-$\beta$3가 B cell 분화에서 중요한 조절인자로 작용할지는 좀 더 연구되어야 할 것이다.

Keywords

References

  1. Biochemistry. v.32 Transforming growth factor β1:secondary structure as determined by heteronuclear magnetic resonance spectroscopy Archer, S.J.;A. Bax;A.B. Roberts;M.B. Sporn;Y.Ogawa;K.A. Piez;J.A. Weatherbee;M.L.-S. Tsang;R.Lucas;B.-L.Zheng;J. Wenker;D.A. Torchia
  2. Eur. J. Surg. v.577 The role of growth factors in peritoneal healing: transforming growth factor β(TGF-β) Chegini, N.
  3. Scand. J. Gastroenterol v.32 Recombinant human transforming growth factor beta 3 accelerates gastric ulcer healing in rats. Coerper, S.;E. Sigloch;D.Cox;M. Starlinger;G. Koveker;H.-D. Becker
  4. J. Exp. Med. v.170 Transforming growth factor-β specifically enhances IgA production by lipopolysaccharide stimulated murine B lymphocytes Coffman, R.L.;D.A. Lebman;B. Shrader
  5. J. Immunol. Methods v.65 A solid-phase enzyme-linked immunospot(ELISPOT) assay for enumeration of specific antibody secreting cell. Czerkinsky, C.C.;L.A. Nilsson;H. Nygren;O. Oucherlony;A. Tarkowski
  6. J. Exp. Med. v.175 Interleukin-10 and transforming growth factor cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A. Defrance, T.;B. Vanbervliet;F. Briere;L. Durand;F. Rousset;J. Banchereau
  7. The EMBO J. v.7 A new type of transforming growth factor-beta, TGF-β3 Derynck, R.;P.B.Lindquist;A.Lee;D.Wen;J.Tamm;J.L.Graycar;L.Rhee;A.J.Mason;D.A.Miller;R.J.Coffey;H.L.Moses;E.Y.Chen
  8. Eur. J. Immunol. v.26 Differential effects of transforming growth factor-β1 on IgA vs. IgG2b production by lipopolysaccharide-simulated lymph node B cells : a comparative study with spleen B cells Garcia, B.;Rodriguez;I. Anglo;A.W.heath;M.C. Howard;J.L. Subiza
  9. J. Immunol. v.145 Transforming growth factor beta 1 increase IgA isotype switching at the clonal level Kim, P. H.;M.F. Kagnoff
  10. J. Leuko. Biol. v.55 Transforming growth factor beta : a matter of life and death McCartney-Francis,N.L.;S.M.Wahl
  11. J. Exp. Med. v.177 Transforming growth factor beta 1 selectively stimulates immunoglobulin G2b secretion by lipopolysaccharide-activated murine B cells. McIntyre, T.M.;D.R. Klinman;P. Rothman;M. Lugo;J.R. Dasch;J.J. Mond;C.M. Snapper
  12. Cell v.63 TGF-beta stimulation and inhibition of cell proliferation : new mechanistic insights Moses, H. L.;E.Y. Yang;J.A. Pietenpol
  13. J. Immunol. v.139 Interleukin 5 and interleukin 4 produced by Peyer's patch T cells selectively enhance immunoglobulin A expression Murray, P.D.;Mckenzie;S.L. Swain;M.F. Kagnoff
  14. J. Biol. Chem. v.271 Binding affinity of transforming growth factor-β for its type Ⅱ receptor is determined by the C-terminal region of the molecule Qian, S. W.;J.K. Burmester;M.L.-S. Tasng;J.A. Weatherbee;A.P. Hinck;D.J. Ohlsen;M.B.Sporn;A.B.Roberts
  15. Handbook of Experimental Pharmacology. Peptide Growth Factors and Their receptors v.95 The transforming growth factor-β. Roberts, A. B.;M.B. Sporn;Sporn, M.B.;A. B. Roberts(eds.)
  16. J. Immunol. v.151 Transforming growth factor-beta1 is required for secretion for IgG of all subclasses by LPS-activated murine B cells in vitro Snapper, C. M.;W. Waegell;H. Beernink;J.R.Dasch