The NOD/SCID chimeric mouse model of human B cell development: studies on the VH4 family immunoglobulin repertoire and implications for SLE

Abstract

The use of the NOD=SCID mouse as a transplant recipient for human cord blood B cell progenitorsas a tool for investigations into the development of human B cells has become an exciting reality. The characteristics of the immunoglobulin repertoire in such a model is important to investigate, as it is possiblethat normal or skewed representationscould be produced.Here we reviewour current work in which we describe a normal VH4 repertoire produced in this chimeric mouse model and describe the differences in combinatorial diversity between the human cells that were isolated from the bone marrow and spleen. The implications of this model for studies of systemic lupus erythematosus are also discussed.

Keywords

NOD/SCID mice cord blood immunoglobulinrepertoire systemic lupus erythematosus

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References

Greiner DL , Hesselton RA , Shultz LD. SCID mouse models of human stem cell engraftment . Stem Cells 1998; 16: 166-177 .

Grabstein KH , Waldschmidt TJ , Finkelman FD et al. Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody . J Exp Med 1993; 178: 257-264 .

Prieyl JA , LeBien TW. Interleukin 7 independent development of human B cells . Proc Natl Acad Sci USA 1996; 93: 10348-10353 .

Blunt T , Finnie NJ , Taccioli GE et al. Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation . Cell 1995; 80: 813-823 .

Shultz LD , Schweitzer PA , Christianson SW et al. Multiple defects in innate and adaptive immunologic function in NOD=LtSz-scid mice . J Immunol 1995; 154: 180-191 .

Hesselton RM , Greiner DL , Mordes JP , Rajan TV , Sullivan JL , Shultz LD. High levels of human peripheral blood mononuclear cell engraftment and enhanced susceptibility to human immunodeficiency virus type 1 infection in NOD=LtSz-scid=scid mice . J Infect Dis 1995; 172: 974-982 .

Hogan CJ , Shpall EJ , McNulty O et al. Engraftment and development of human CD34()-enriched cells from umbilical cord blood in NOD=LtSz-scid=scid mice . Blood 1997; 90: 85-96 .

Rossi MI , Medina KL , Garrett K et al. Relatively normal human lymphopoiesisbut rapid turnover of newly formed B cells in transplanted nonobese diabetic=SCID mice . J Immunol 2001; 167: 3033-3042 .

Martin F , Kearney JF. B1 cells: similarities and differences with other B cell subsets . Curr Opin Immunol 2001; 13: 195-201 .

10.

Novelli EM , Ramirez M , Leung W , Civin CI. Human hematopoietic stem=progenitor cells generate CD5 B lymphoid cells in NOD=SCID mice . Stem Cells 1999; 17: 242-252 .

11.

Potter KN , Li Y , Pascual V et al. Molecular characterization of a cross-reactive idiotope on human immunoglobulinsutilizing the VH4-21 gene segment . J Exp Med 1993; 178: 1419-1428 .

12.

Friedman DF , Kraj P , Silberstein LE. VH4.21 expression in the normal human B-cell repertoire . Ann NY Acad Sci 1995; 764: 285-292 .

13.

Pascual V , Verkruyse L , Casey ML , Capra JD. Analysis of Ig H chain gene segment utilization in human fetal liver. Revisiting the “proximal utilization hypothesis” . J Immunol 1993; 151: 4164-4172 .

14.

Mortari F , Newton JA , Wang JY , Schroeder HWJ. The human cord blood antibody repertoire. Frequent usage of the VH7 gene family . Eur J Immunol 1992; 22: 241-245 .

15.

Shiokawa S , Mortari F , Lima JO et al. IgM heavy chain complementarity-determining region 3 diversity is constrained by genetic and somatic mechanisms until two months after birth . J Immunol 1999; 162: 6060-6070 .

16.

Schroeder HWJ , Zhang L , Philips JBR. Slow, programmed maturation of the immunoglobulinHCDR3 repertoire during the third trimester of fetal life . Blood 2001; 98: 2745-2751 .

17.

Pascual V , Victor K , Spellerberg M , Hamblin TJ , Stevenson FK , Capra JD. VH restriction among human cold agglutinins. The VH4-21 gene segment is required to encode anti-I and anti-i specificities . J Immunol 1992; 149: 2337-2344 .

18.

Thompson KM , Sutherland J , Barden G et al. Human monoclonal antibodies against blood group antigens preferentially express a VH4-21 variable region gene-associated epitope . Scand J Immunol 1991; 34: 509-518 .

19.

Pascual V , Victor K , Lelsz D et al. Nucleotide sequence analysis of the V regions of two IgM cold agglutinins. Evidence that the VH4-21 gene segment is responsible for the major cross-reactive idiotype . J Immunol 1991; 146: 4385-4391 .

20.

Isenberg D , Spellerberg M , Williams W , Griffiths M , Stevenson F. Identification of the 9G4 idiotope in systemic lupus erythematosus . Br J Rheumatol 1993; 32: 876-882 .

21.

van VRF , Bieber MM , Powell MJ et al. VH4-34 encoded antibodies in systemic lupus erythematosus: a specific diagnostic marker that correlates with clinical disease characteristics . J Rheumatol 1999; 26: 1727-1733 .

22.

McCune JM , Namikawa R , Kaneshima H , Shultz LD , Lieberman M , Weissman IL. The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function . Science 1988; 241: 1632-1639 .

23.

McClain MT , Harley JB , James JA. The role of Epstein-Barr virus in systemic lupus erythematosus . Front Biosci 2001; 6: E137-E147 .

24.

James JA , Neas BR , Moser KL et al. Systemic lupus erythematosus in adults is associated with previous Epstein-Barr virus exposure . Arthritis Rheum 2001; 44: 1122-1126 .

25.

James JA , Kaufman KM , Farris AD , Taylor-Albert E , Lehman TJ , Harley JB. An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus . J Clin Invest 1997; 100: 3019-3026 .

26.

Fagarasan S , Honjo T. T-Independent immune response: new aspects of B cell biology . Science 2000; 290: 89-92 .

27.

Ravetch JV , Lanier LL. Immune inhibitory receptors . Science 2000; 290: 84-89 .

28.

Hardy RR , Hayakawa K , Shimizu M , Yamasaki K , Kishimoto T. Rheumatoid factor secretion from human Leu-1 B cells . Science 1987; 236: 81-83 .

29.

Hardy RR , Li YS , Hayakawa K. Distinctive developmental origins and specificities of the CD5 B-cell subset . Semin Immunol 1996; 8: 37-44 .

30.

Kaplan D , Smith D , Meyerson H , Pecora N , Lewandowska K. CD5 expression by B lymphocytes and its regulation upon Epstein-Barr virus transformation . Proc Natl Acad Sci USA 2001; 98: 13850-13853 .