Haochu Huang, Ph.D.

B Cell Tolerance and Activation in Autoimmunity

Research Summary

Our laboratory is interested in understanding how autoreactive T and B cells are regulated in normal immune system and what goes wrong in autoimmunity. We have been exploiting transgenic and gene-targeting technology to engineer new mouse models for rheumatoid arthritis. Major questions tackled are why tolerance fails in these models, what triggers the autoimmune processes, how genetic background affects tolerance, and differential signaling by B cell receptor in tolerance induction. Most recently, we have been utilizing our mouse models to understand the mechanisms of B cell-depletion therapy by rituximab, which is effective in treating rheumatoid arthritis and other autoimmune diseases.

Selected Papers

Huang H, Marsh-Armstrong N and Brown DD. (1999) Metamorphosis is inhibited in transgenic Xenopus laevis tadpoles that overexpress type III deiodinase.  Proc. Natl. Acad. Sci. USA, 96(3):962-7.

Marsh-Armstrong N, Huang H, Berry DL and Brown DD. (1999) Germ-line transmission of transgenes in Xenopus laevis.  Proc. Natl. Acad. Sci. USA, 96(25): 14389-14393.

Marsh-Armstrong N, Huang H, Remo BF, Liu T and Brown DD. (1999) Asymmetric growth and development of the Xenopus laevis retina during metamorphosis is controlled by type-III deiodinase.  Neuron, 24: 871-878.
                     
Huang H and Brown DD. (2000) Overexpression of Xenopus laevis growth hormone stimulates growth of tadpoles and frogs.  Proc. Natl. Acad. Sci. USA, 97(1): 190-194.

Huang H and Brown DD. (2000) Prolactin is not a juvenile hormone in Xenopus laevis metamorphosis.  Proc. Natl. Acad. Sci. USA, 97(1): 195-199.

Huang H, Cai L, Remo BF and Brown DD. (2001) Timing of metamorphosis and the onset of the negative feedback loop between the thyroid gland and the pituitary is controlled by type II iodothyronine deiodinase in Xenopus laevis.  Proc Natl Acad Sci USA. 98(13):7348-53.

Schreiber AM, Das B, Huang H, Marsh-Armstrong N and Brown DD. (2001) Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a dominant negative thyroid hormone receptor. Proc Natl Acad Sci USA.98 (19):10739-44.

Das B, Schreiber AM, Huang H and Brown DD. (2002) Multiple thyroid hormone-induced muscle growth and death programs during metamorphosis in Xenopus laevis.  Proc Natl Acad Sci USA 99(19):12230-5.

Maccioni M, Zeder-Lutz G, Huang H, Ebel C, Gerber P, Hergueux J, Marchal P, Duchatelle V, Degott C, van Regenmortel M, Benoist C and Mathis D. (2002) Arthritogenic monoclonal antibodies from K/BxN mice. J Exp Med 195(8):1071-7.

Huang H, Kearney JF, Grusby M, Benoist C and Mathis D. (2006) Induction of tolerance in arthritogenic B cells with receptors of differing affinity for self-antigen. Proc Natl Acad Sci USA 103(10): 3734-9.

Monach P, Hattori K, Huang H, Hyatt E, Morse J, Nguyen L, Ortiz-Lopez A, Wu HJ, Mathis D, Benoist C. The K/BxN mouse model of inflammatory arthritis: theory and practice. Methods Mol Med. 2007;136:269-82.

Huang H, Benoist C and Mathis, D. Rituximab specifically depletes short-lived autoreactive plasma cells in a mouse model of inflammatory arthritis. Proc Natl Acad Sci USA 2010; 107: 4658-63. (Comment in: Nat Rev Rheumatol. 2010; 6(5): 246).