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International Immunology, Vol. 5, No. 6, pp. 647-656,June 1993
© 1993 Japanese Society for Immunology
Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus
The Howard Hughes Medical Institute, Children's Hospital and the Department of Genetics, Harvard Medical School and Center for Blood Research 300 Longwood Avenue, Boston, MA 02115, USA
1 GenPharm International Inc. 297 North Bernado Avenue, Mountain View, CA 94043, USA
Correspondence to: Correspondence to: D. Huszar
B lymphocyte differentiation is characterized by an ordered series of Ig gene assembly and expression events. In the majority of normal B cells, assembly and expression of Ig heavy (H) chain genes precedes that of light (L) chain genes. To determine the role of the Ig heavy chain protein in B cell development and L chain gene rearrangement, we have generated mice that cannot assemble Ig H chain genes as a result of targeted deletion of the JH gene segments in embryonic stem cells. Mice homozygous for this deletion are devoid of slg+ B cells in the bone marrow and periphery. B cell differentiation in these mice is blocked at the large, CD43+ precursor stage. However, these precursor B cells do assemble 
L chain genes at a low level in the absence of µ H chain proteins. These data demonstrate that rearrangement and expression of the µ H chain gene is not absolutely required for L chain gene rearrangement in vivo. Expression of µ chains may facilitate either efficient L chain gene rearrangement or the survival of cells that have rearranged light chain genes by promoting the differentiation of large, CD43+ to small, CD43– pre-B cells.
Keywords: B cell deficient mice, B cell development, Ig gene rearrangement, JH locus, targeted mutation
Received 16 February 1993, accepted 4 March 1993.
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K. Maki, K. Nagata, F. Kitamura, T. Takemori, and H. Karasuyama Immunoglobulin {beta} Signaling Regulates Locus Accessibility for Ordered Immunoglobulin Gene Rearrangements J. Exp. Med., April 17, 2000; 191(8): 1333 - 1340. [Abstract] [Full Text] [PDF]
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P. E. Kima, S. L. Constant, L. Hannum, M. Colmenares, K. S. Lee, A. M. Haberman, M. J. Shlomchik, and D. McMahon-Pratt Internalization of Leishmania mexicana Complex Amastigotes via the Fc Receptor Is Required to Sustain Infection in Murine Cutaneous Leishmaniasis J. Exp. Med., March 20, 2000; 191(6): 1063 - 1068. [Abstract] [Full Text] [PDF]
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P. C. Sayles, G. W. Gibson, and L. L. Johnson B Cells Are Essential for Vaccination-Induced Resistance to Virulent Toxoplasma gondii Infect. Immun., March 1, 2000; 68(3): 1026 - 1033. [Abstract] [Full Text] [PDF]
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O. T. M. Chan and M. J. Shlomchik Cutting Edge: B Cells Promote CD8+ T Cell Activation in MRL-Faslpr Mice Independently of MHC Class I Antigen Presentation J. Immunol., February 15, 2000; 164(4): 1658 - 1662. [Abstract] [Full Text] [PDF]
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 T. V. Golovkina, M. Shlomchik, L. Hannum, and A. Chervonsky Organogenic Role of B Lymphocytes in Mucosal Immunity Science, December 3, 1999; 286(5446): 1965 - 1968. [Abstract] [Full Text]
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O. T. M. Chan, M. P. Madaio, and M. J. Shlomchik B Cells Are Required for Lupus Nephritis in the Polygenic, Fas-Intact MRL Model of Systemic Autoimmunity J. Immunol., October 1, 1999; 163(7): 3592 - 3596. [Abstract] [Full Text] [PDF]
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A. M. Oliver, F. Martin, and J. F. Kearney IgMhighCD21high Lymphocytes Enriched in the Splenic Marginal Zone Generate Effector Cells More Rapidly Than the Bulk of Follicular B Cells J. Immunol., June 15, 1999; 162(12): 7198 - 7207. [Abstract] [Full Text] [PDF]
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W. P. Weidanz, J. R. Kemp, J. M. Batchelder, F. K. Cigel, M. Sandor, and H. C. v. d. Heyde Plasticity of Immune Responses Suppressing Parasitemia During Acute Plasmodium chabaudi Malaria J. Immunol., June 15, 1999; 162(12): 7383 - 7388. [Abstract] [Full Text] [PDF]
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O. T.M. Chan, L. G. Hannum, A. M. Haberman, M. P. Madaio, and M. J. Shlomchik A Novel Mouse with B Cells but Lacking Serum Antibody Reveals an Antibody-independent Role for B Cells in Murine Lupus J. Exp. Med., May 17, 1999; 189(10): 1639 - 1648. [Abstract] [Full Text] [PDF]
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A. C. Shaw, W. Swat, L. Davidson, and F. W. Alt Induction of Ig light chain gene rearrangement in heavy chain-deficient B cells by activated Ras PNAS, March 2, 1999; 96(5): 2239 - 2243. [Abstract] [Full Text] [PDF]
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C. P. Wong, C. Y. Okada, and R. Levy TCR Vaccines Against T Cell Lymphoma: QS-21 and IL-12 Adjuvants Induce a Protective CD8+ T Cell Response J. Immunol., February 15, 1999; 162(4): 2251 - 2258. [Abstract] [Full Text] [PDF]
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T. I. Novobrantseva, V. M. Martin, R. Pelanda, W. Muller, K. Rajewsky, and A. Ehlich Rearrangement and Expression of Immunoglobulin Light Chain Genes Can Precede Heavy Chain Expression during Normal B Cell Development in Mice J. Exp. Med., January 4, 1999; 189(1): 75 - 88. [Abstract] [Full Text] [PDF]
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D. R. Brown and S. L. Reiner Polarized Helper-T-Cell Responses against Leishmania major in the Absence of B Cells Infect. Immun., January 1, 1999; 67(1): 266 - 270. [Abstract] [Full Text] [PDF]
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G. H. Kline, L. Hartwell, G. B. Beck-Engeser, U. Keyna, S. Zaharevitz, N. R. Klinman, and H.-M. Jack Pre-B Cell Receptor-Mediated Selection of Pre-B Cells Synthesizing Functional {micro} Heavy Chains J. Immunol., August 15, 1998; 161(4): 1608 - 1618. [Abstract] [Full Text] [PDF]
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F. E. Cronin, M. Jiang, A. K. Abbas, and S. A. Grupp Role of {micro} Heavy Chain in B Cell Development. I. Blocked B Cell Maturation But Complete Allelic Exclusion in the Absence of Ig{alpha}/{beta} J. Immunol., July 1, 1998; 161(1): 252 - 259. [Abstract] [Full Text] [PDF]
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D. E. Elliott, A. M. Blum, J. Li, A. Metwali, and J. V. Weinstock Preprosomatostatin Messenger RNA Is Expressed by Inflammatory Cells and Induced by Inflammatory Mediators and Cytokines J. Immunol., April 15, 1998; 160(8): 3997 - 4003. [Abstract] [Full Text] [PDF]
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H. T. Maecker, M.-S. Do, and S. Levy CD81 on B cells promotes interleukin 4 secretion and antibody production during T helper type 2 immune responses PNAS, March 3, 1998; 95(5): 2458 - 2462. [Abstract] [Full Text] [PDF]
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M. Cascalho, J. Wong, C. Steinberg, and M. Wabl Mismatch Repair Co-opted by Hypermutation Science, February 20, 1998; 279(5354): 1207 - 1210. [Abstract] [Full Text]
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A. E. Macaulay, R. H. DeKruyff, and D. T. Umetsu Antigen-Primed T Cells from B Cell-Deficient JHD Mice Fail to Provide B Cell Help J. Immunol., February 15, 1998; 160(4): 1694 - 1700. [Abstract] [Full Text] [PDF]
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Y. Minegishi, E. Coustan-Smith, Y.-H. Wang, M. D. Cooper, D. Campana, and M. E. Conley Mutations in the Human {lambda}5/14.1 Gene Result in B Cell Deficiency and Agammaglobulinemia J. Exp. Med., January 5, 1998; 187(1): 71 - 77. [Abstract] [Full Text] [PDF]
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O. Chan and M. J. Shlomchik A New Role for B Cells in Systemic Autoimmunity: B Cells Promote Spontaneous T Cell Activation in MRL-lpr/lpr Mice J. Immunol., January 1, 1998; 160(1): 51 - 59. [Abstract] [Full Text] [PDF]
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 L. H. Chow, S. Huh, J. Jiang, R. Zhong, and J. G. Pickering Intimal Thickening Develops Without Humoral Immunity in a Mouse Aortic Allograft Model of Chronic Vascular Rejection Circulation, December 15, 1996; 94(12): 3079 - 3082. [Abstract] [Full Text]
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 L. Yel, Y. Minegishi, E. Coustan-Smith, R. H. Buckley, H. Trubel, L. M. Pachman, G. R. Kitchingman, D. Campana, J. Rohrer, and M. E. Conley Mutations in the Mu Heavy-Chain Gene in Patients with Agammaglobulinemia N. Engl. J. Med., November 14, 1996; 335(20): 1486 - 1493. [Abstract] [Full Text] [PDF]
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