Hormonal regulation of B-cell function and systemic lupus erythematosus

Abstract

The prevalence of systemic lupus erythematosus (SLE) is far higher in females than in males and numerous investigations to understand this gender bias have been performed, which propose as casual actors genetic predispositions and sex hormones effects. We will describe in this review how the sex hormones estrogen and prolactin influence B cell maturation and selection, permitting B cells to mature to immunocompetence in a mouse model of lupus. Finally, we will discuss the relevance and implications of these results for human disease.

Get full access to this article

View all access options for this article.

References

1 Boumpas DT Austin HA Fessler BJ Balow JE Klippel JH Lockshin MD . Systemic lupus erythematosus: emerging concepts. Part 1: renal, neuropsychiatric, cardiovascular, pulmonary, and hematologic disease. Ann Intern Med 1995; 122: 940 – 950 .

2 Cervera R Khamashta MA Font J . Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore) 1993; 72: 113 – 124 .

3 Cohen-Solal JF Jeganathan V Grimaldi CM Peeva E Diamond B . Sex hormones and SLE: influencing the fate of autoreactive B cells. Curr Top Microbiol Immunol 2006; 305: 67 – 88 .

4 Medina KL Smithson G Kincade PW . Suppression of B lymphopoiesis during normal pregnancy. J Exp Med 1993; 178: 1507 .

5 Medina KL Kincade PW . Pregnancy-related steroids are potential regulators of B lymphopoiesis. Proc Natl Acad Sci USA 1994; 91: 5382 .

6 Masuzawa T Miyaura C Onoe Y . Estrogen deficiency stimulates B lymphopoiesis in mouse bone marrow. J Clin Invest 1994; 94: 1090 – 1097 .

7 Viselli SM Reese KR Fan J . Kovacs, WJ, Olsen, NJ. Androgens alter B cell development in normal male mice. Cell Immunol 1997; 182: 99 – 104 .

8 Ellis TM Moser MT Le PT Flanigan RC Kwon ED . Alterations in peripheral B cells and B cell progenitors following androgen ablation in mice. Int Immunol 2001; 13: 553 – 558 .

9 Miyaura C Onoe Y Inada M . Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function: similarity to estrogen deficiency. Proc Natl Acad Sci USA 1997; 94: 9360 – 9365 .

10.

10 Smithson G Beamer WG Ponting I Kincade PW . Estrogen suppresses stromal cell-dependent lymphopoiesis in culture. J Immunol 1995; 155: 3409 .

11.

11 Olsen NJ Gu X Kovacs WJ . Bone marrow stromal cells mediate androgenic suppression of B lymphocyte development. J Clin Invest 2001; 108: 1697 – 1704 .

12.

12 Offen D Spatz L Escowitz H Factor S Diamond B . Induction of tolerance to an IgG autoantibody. Proc Natl Acad Sci USA 1992; 89: 8332 – 8336 .

13.

13 Spatz L Saenko V Iliev A Jones L Geskin L Diamond B . Light chain usage in anti-double-stranded DNA B cell subsets: role in cell fate determination. J Exp Med 1997; 185: 1317 – 1326 .

14.

14 Bynoe MS Spatz L Diamond B . Characterization of anti-DNA B cells that escape negative selection. Eur J Immunol 1999; 29: 1304 – 1313 .

15.

15 Kuo P Bynoe MS Wang C Diamond B . Bcl-2 leads to expression of anti-DNA B cells but no nephritis: a model for a clinical subset. Eur J Immunol 1999; 29: 3168 – 3178 .

16.

16 Medina KL Garrett KP Thompson LF Rossi MI Payne KJ Kincade PW . Identification of very early lymphoid precursors in bone marrow and their regulation by estrogen. Nat Immunol 2001; 2: 718 – 724 .

17.

17 Grimaldi CM Michael DJ Diamond B . Cutting edge: expansion and activation of a population of autoreactive marginal zone B cells in a model of estrogen-induced lupus. J Immunol 2001; 167: 1886 – 1890 .

18.

18 Grimaldi CM Cleary J Dagtas AS Moussai D Diamond B . Estrogen alters thresholds for B cell apoptosis and activation. J Clin Invest 2002; 109: 1625 – 1633 .

19.

19 Grimaldi CM; Diamond B; . (unpublished results).

20.

20 Grimaldi CM Jeganathan V Diamond B . Hormonal regulation of B cell development: 17 beta-estradiol impairs negative selection of high-affinity DNA-reactive B cells at more than one developmental checkpoint. J Immunol 2006; 176: 2703 – 2710 .

21.

21 Shaw PX Horkko S Chang MK . Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity. J Clin Invest 2000; 105: 1731 – 1740 .

22.

22 Hande S Notidis E Manser T . Bcl-2 obstructs negative selection of autoreactive, hypermutated antibody V regions during memory B cell development. Immunity 1998; 8: 189 – 198 .

23.

23 Grimaldi CM Hicks R Diamond B . B cell selection and susceptibility to autoimmunity. J Immunol 2005; 174: 1775 – 1781 .

24.

24 Morales P Carretero MV Geronimo H . Influence of prolactin on the differentiation of mouse B-lymphoid precursors. Cell Growth Differ 1999; 10: 583 – 590 .

25.

25 Steger RW Chandrashekar V Zhao W Bartke A Horseman ND . Neuroendocrine and reproductive functions in male mice with targeted disruption of the prolactin gene. Endocrinology 1998; 139: 3691 – 3695 .

26.

26 Bouchard B Ormandy CJ Di Santo JP Kelly PA . Immune system development and function in prolactin receptor-deficient mice. J Immunol 1999; 163: 576 – 582 .

27.

27 McMurray R Keisler D Izui S Walker SE . Hyperprolactinemia in male NZB/NZW (B/W) F1 mice: accelerated autoimmune disease with normal circulating testosterone. Clin Immunol Immunopathol 1994; 71: 338 – 343 .

28.

28 McMurray R Keisler D Kanuckel K Izui S Walker SE . Prolactin influences autoimmune disease activity in the female B/W mouse. J Immunol 1991; 147: 3780 – 3787 .

29.

29 Peeva E Michael D Cleary J Rice J Chen X Diamond B . Prolactin modulates the naive B cell repertoire. J Clin Invest 2003; 111: 275 – 283 .

30.

30 Ratkay LG Weinberg J Waterfield JD . The effect of lactation in the post-partum arthritis of MRL-lpr/fasmice. Rheumatology (Oxford) 2000; 39: 646 – 651 .

31.

31 Walker SE . Bromocriptine treatment of systemic lupus erythematosus. Lupus 2001; 10: 762 – 768 .

32.

32 Peeva E Grimaldi C Spatz L Diamond B . Bromocriptine restores tolerance in estrogen-treated mice. J Clin Invest 2000; 106: 1373 – 1379 .

33.

33 Venkatesh J Peeva E Xu X Diamond B . Cutting edge: hormonal milieu, not antigenic specificity, determines the mature phenotype of autoreactive B cells. J Immunol 2006; 176: 3311 – 3314 .

34.

34 Peeva E Venkatesh J Michael D Diamond B . Prolactin as a modulator of B cell function: implications for SLE. Biomed Pharmacother 2004; 58: 310 – 319 .

35.

35 Neidhart M . Bromocriptine has little direct effect on murine lymphocytes, the immunomodulatory effect being mediated by the suppression of prolactin secretion. Biomed Pharmacother 1997; 51: 118 – 125 .

36.

36 Inui A Ogasawara H Naito T . Estrogen receptor expression by peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Clin Rheumatol 2007; 26: 1675 – 1678 .

37.

37 Phiel KL Henderson RA Adelman SJ Elloso MM . Differential estrogen receptor gene expression in human peripheral blood mononuclear cell populations. Immunol Lett 2005; 97: 107 – 113 .

38.

38 Kanda N Tamaki K . Estrogen enhances immunoglobulin production by human PBMCs. J Allergy Clin Immunol 1999; 103 (2 Pt 1): 282 – 288 .

39.

39 Evans MJ MacLaughlin S Marvin RD Abdou NI . Estrogen decreases in vitro apoptosis of peripheral blood mononuclear cells from women with normal menstrual cycles and decreases TNF-alpha production in SLE but not in normal cultures. Clin Immunol Immunopathol 1997; 82: 258 – 262 .

40.

40 Sandi C Cambronero JC Borrell J Guaza C . Mutually antagonistic effects of corticosterone and prolactin on rat lymphocyte proliferation. Neuroendocrinology 1992; 56: 574 – 581 .

41.

41 Krumenacker JS Buckley DJ Leff MA . Prolactin-regulated apoptosis of Nb2 lymphoma cells: pim-1, bcl-2, and bax expression. Endocrine 1998; 9: 163 – 170 .

42.

42 Allen SH Sharp GC Wang G . Prolactin levels and antinuclear antibody profiles in women tested for connective tissue disease. Lupus 1996; 5: 30 – 37 .

43.

43 Gutierrez MA Molina JF Jara LJ . Prolactin-induced immunoglobulin and autoantibody production by peripheral blood mononuclear cells from systemic lupus erythematosus and normal individuals. Int Arch Allergy Immunol 1996; 109: 229 – 235 .

44.

44 Jacobi AM Rohde W Volk HD Dorner T Burmester GR Hiepe F . Prolactin enhances the in vitro production of IgG in peripheral blood mononuclear cells from patients with systemic lupus erythematosus but not from healthy controls. Ann Rheum Dis 2001; 60: 242 – 247 .

45.

45 Cesario TC Yousefi S Carandang G Sadati N Le J Vaziri N . Enhanced yields of gamma interferon in prolactin treated human peripheral blood mononuclear cells. Proc Soc Exp Biol Med 1994; 205: 89 – 95 .

46.

46 Roubinian JR Talal N Greenspan JS Goodman JR Siiteri PK . Delayed androgen treatment prolongs survival in murine lupus. J Clin Invest 1979; 63: 902 – 911 .

47.

47 Carlsten H Tarkowski A Holmdahl R Nilsson LA . Oestrogen is a potent disease accelerator in SLE-prone MRL lpr/lpr mice. Clin Exp Immunol 1990; 80: 467 – 473 .

48.

48 Carlsten H Nilsson N Jonsson R Backman K Holmdahl R Tarkowski A . Estrogen accelerates immune complex glomerulonephritis but ameliorates T cell-mediated vasculitis and sialadenitis in autoimmune MRL lpr/lpr mice. Cell Immunol 1992; 144: 190 – 202 .

49.

49 Dhaher YY Greenstein BD Khamashta MA Hughes GR . Effects of oestradiol and the oestrogen antagonist Ici 182,780 on the delayed type hypersensitivity (DTH) index and on serum levels of IgM and IgG in ovariectomised Balb/C and MRL/Mp-Lpr/Lpr mice, a model of systemic lupus erythematosus (SLE). Autoimmunity 2001; 33: 237 – 243 .

50.

50 Auborn KJ Qi M Yan XJ . Lifespan is prolonged in autoimmune-prone (NZB/NZW) F1 mice fed a diet supplemented with indole-3-carbinol. J Nutr 2003; 133: 3610 – 3613 .

51.

51 Pimstone BL. S.L.E . cells after oral contraceptives. Lancet 1968; 25: 1153 .

52.

52 Chapel TA Burns RE . Oral contraceptives and exacerbation of lupus erythematosus. Am J Obstet Gynecol 1971; 110: 366 – 369 .

53.

53 Travers RL Hughes GR . Oral contraceptive therapy and systemic lupus erythematosus. J Rheumatol 1978; 5: 448 – 451 .

54.

54 Garovich M Agudelo C Pisko E . Oral contraceptives and systemic lupus erythematosus. Arthritis Rheum 1980; 23: 1396 – 1398 .

55.

55 Furukawa F Tachibana T Imamura S Tamura T . Oral contraceptive-induced lupus erythematosus in a Japanese woman. J Dermatol 1991; 18: 56 – 58 .

56.

56 Barrett C Neylon N Snaith ML . Oestrogen-induced systemic lupus erythematosus. Br J Rheumatol 1986; 25: 300 – 301 .

57.

57 Jungers P Liote F Dehaine V . [Hormonal contraception and lupus] in French. Ann Med Interne (Paris) 1990; 141: 253 – 256 .

58.

58 Julkunen HA . Oral contraceptives in systemic lupus erythematosus: side-effects and influence on the activity of SLE. Scand J Rheumatol 1991; 20: 427 – 433 .

59.

59 Buyon JP Belmont HM Kalunian KC . Postmenopausal hormone therapy and systemic lupus erythematosus. Ann Intern Med 1995; 123: 961 .

60.

60 Arden NK Lloyd ME Spector TD Hughes GR . Safety of hormone replacement therapy (HRT) in systemic lupus erythematosus (SLE). Lupus 1994; 3: 11 – 13 .

61.

61 Kreidstein S Urowitz MB Gladman DD Gough J . Hormone replacement therapy in systemic lupus erythematosus. J Rheumatol 1997; 24: 2149 – 2152 .

62.

62 Mok CC Lau CS Ho CT Lee KW Mok MY Wong RW . Safety of hormonal replacement therapy in postmenopausal patients with systemic lupus erythematosus. Scand J Rheumatol 1998; 27: 342 – 346 .

63.

63 Sanchez-Guerrero J Liang MH Karlson EW Hunter DJ Colditz GA . Postmenopausal estrogen therapy and the risk for developing systemic lupus erythematosus. Ann Intern Med 1995; 122: 430 – 433 .

64.

64 Sanchez-Guerrero J Karlson EW Liang MH Hunter DJ Speizer FE Colditz GA . Past use of oral contraceptives and the risk of developing systemic lupus erythematosus. Arthritis Rheum 1997; 40: 804 – 808 .

65.

65 Buyon JP Petri MA Kim MY . The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial. Ann Intern Med 2005; 142: 953 – 962 .

66.

66 Petri M Kim MY Kalunian KC . OC-SELENA Trial. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005; 353: 2550 – 2558 .