Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. 1998 Aug 15; 102(4): 853–860.
PMCID: PMC508949

Absence of IgD-CD27(+) memory B cell population in X-linked hyper-IgM syndrome.


The present study analyzed peripheral blood B cell populations separated by IgD and CD27 expression in six males with X-linked hyper-IgM syndrome (XHIM). Costimulation of mononuclear cells from most of the patients induced no to low levels of class switching from IgM to IgG and IgA with Staphylococcus aureus Cowan strain (SAC) plus IL-2 or anti-CD40 mAb (anti-CD40) plus IL-10. Measurable levels of IgE were secreted in some of the patients after stimulation with anti-CD40 plus IL-4. Costimulation with SAC plus IL-2 plus anti-CD40 plus IL-10 yielded secretion of significant levels of IgG in addition to IgM, but not IgA. The most striking finding was that peripheral blood B cells from all of the six patients were composed of only IgD+ CD27(-) and IgD+ CD27(+) B cells; IgD- CD27(+) memory B cells were greatly decreased. IgD+ CD27(+) B cells from an XHIM patient produced IgM predominantly. Our data indicate that the low response of IgG production in XHIM patients is due to reduced numbers of IgD- CD27(+) memory B cells. However, the IgG production can be induced by stimulation of immunoglobulin receptors and CD40 in cooperation with such cytokines as IL-2 and IL-10 in vitro.

Full Text

The Full Text of this article is available as a PDF (294K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • ROSEN FS, KEVY SV, MERLER E, JANEWAY CA, GITLIN D. Recurrent bacterial infections and dysgamma-globulinemia: deficiency of 7S gamma-globulins in the presence of elevated 19S gamma-globulins. Report of two cases. Pediatrics. 1961 Aug;28:182–195. [PubMed]
  • Callard RE, Armitage RJ, Fanslow WC, Spriggs MK. CD40 ligand and its role in X-linked hyper-IgM syndrome. Immunol Today. 1993 Nov;14(11):559–564. [PubMed]
  • Aruffo A, Farrington M, Hollenbaugh D, Li X, Milatovich A, Nonoyama S, Bajorath J, Grosmaire LS, Stenkamp R, Neubauer M, et al. The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. Cell. 1993 Jan 29;72(2):291–300. [PubMed]
  • Allen RC, Armitage RJ, Conley ME, Rosenblatt H, Jenkins NA, Copeland NG, Bedell MA, Edelhoff S, Disteche CM, Simoneaux DK, et al. CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome. Science. 1993 Feb 12;259(5097):990–993. [PubMed]
  • DiSanto JP, Bonnefoy JY, Gauchat JF, Fischer A, de Saint Basile G. CD40 ligand mutations in x-linked immunodeficiency with hyper-IgM. Nature. 1993 Feb 11;361(6412):541–543. [PubMed]
  • Armitage RJ, Fanslow WC, Strockbine L, Sato TA, Clifford KN, Macduff BM, Anderson DM, Gimpel SD, Davis-Smith T, Maliszewski CR, et al. Molecular and biological characterization of a murine ligand for CD40. Nature. 1992 May 7;357(6373):80–82. [PubMed]
  • Stamenkovic I, Clark EA, Seed B. A B-lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas. EMBO J. 1989 May;8(5):1403–1410. [PMC free article] [PubMed]
  • Banchereau J, Rousset F. Growing human B lymphocytes in the CD40 system. Nature. 1991 Oct 17;353(6345):678–679. [PubMed]
  • Xu J, Foy TM, Laman JD, Elliott EA, Dunn JJ, Waldschmidt TJ, Elsemore J, Noelle RJ, Flavell RA. Mice deficient for the CD40 ligand. Immunity. 1994 Aug;1(5):423–431. [PubMed]
  • van Essen D, Kikutani H, Gray D. CD40 ligand-transduced co-stimulation of T cells in the development of helper function. Nature. 1995 Dec 7;378(6557):620–623. [PubMed]
  • Chu YW, Marin E, Fuleihan R, Ramesh N, Rosen FS, Geha RS, Insel RA. Somatic mutation of human immunoglobulin V genes in the X-linked HyperIgM syndrome. J Clin Invest. 1995 Mar;95(3):1389–1393. [PMC free article] [PubMed]
  • Han S, Hathcock K, Zheng B, Kepler TB, Hodes R, Kelsoe G. Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers. J Immunol. 1995 Jul 15;155(2):556–567. [PubMed]
  • Gray D, Dullforce P, Jainandunsing S. Memory B cell development but not germinal center formation is impaired by in vivo blockade of CD40-CD40 ligand interaction. J Exp Med. 1994 Jul 1;180(1):141–155. [PMC free article] [PubMed]
  • Arpin C, Déchanet J, Van Kooten C, Merville P, Grouard G, Brière F, Banchereau J, Liu YJ. Generation of memory B cells and plasma cells in vitro. Science. 1995 May 5;268(5211):720–722. [PubMed]
  • Nonoyama S, Farrington ML, Ochs HD. Effect of IL-2 on immunoglobulin production by anti-CD40-activated human B cells: synergistic effect with IL-10 and antagonistic effect with IL-4. Clin Immunol Immunopathol. 1994 Sep;72(3):373–379. [PubMed]
  • Rousset F, Garcia E, Defrance T, Péronne C, Vezzio N, Hsu DH, Kastelein R, Moore KW, Banchereau J. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1890–1893. [PMC free article] [PubMed]
  • Gascan H, Gauchat JF, Aversa G, Van Vlasselaer P, de Vries JE. Anti-CD40 monoclonal antibodies or CD4+ T cell clones and IL-4 induce IgG4 and IgE switching in purified human B cells via different signaling pathways. J Immunol. 1991 Jul 1;147(1):8–13. [PubMed]
  • Camerini D, Walz G, Loenen WA, Borst J, Seed B. The T cell activation antigen CD27 is a member of the nerve growth factor/tumor necrosis factor receptor gene family. J Immunol. 1991 Nov 1;147(9):3165–3169. [PubMed]
  • Goodwin RG, Alderson MR, Smith CA, Armitage RJ, VandenBos T, Jerzy R, Tough TW, Schoenborn MA, Davis-Smith T, Hennen K, et al. Molecular and biological characterization of a ligand for CD27 defines a new family of cytokines with homology to tumor necrosis factor. Cell. 1993 May 7;73(3):447–456. [PubMed]
  • Agematsu K, Kobata T, Sugita K, Hirose T, Schlossman SF, Morimoto C. Direct cellular communications between CD45R0 and CD45RA T cell subsets via CD27/CD70. J Immunol. 1995 Apr 15;154(8):3627–3635. [PubMed]
  • Kobata T, Jacquot S, Kozlowski S, Agematsu K, Schlossman SF, Morimoto C. CD27-CD70 interactions regulate B-cell activation by T cells. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11249–11253. [PMC free article] [PubMed]
  • Agematsu K, Kobata T, Yang FC, Nakazawa T, Fukushima K, Kitahara M, Mori T, Sugita K, Morimoto C, Komiyama A. CD27/CD70 interaction directly drives B cell IgG and IgM synthesis. Eur J Immunol. 1995 Oct;25(10):2825–2829. [PubMed]
  • Agematsu K, Nagumo H, Yang FC, Nakazawa T, Fukushima K, Ito S, Sugita K, Mori T, Kobata T, Morimoto C, et al. B cell subpopulations separated by CD27 and crucial collaboration of CD27+ B cells and helper T cells in immunoglobulin production. Eur J Immunol. 1997 Aug;27(8):2073–2079. [PubMed]
  • Agematsu K, Nagumo H, Oguchi Y, Nakazawa T, Fukushima K, Yasui K, Ito S, Kobata T, Morimoto C, Komiyama A. Generation of plasma cells from peripheral blood memory B cells: synergistic effect of interleukin-10 and CD27/CD70 interaction. Blood. 1998 Jan 1;91(1):173–180. [PubMed]
  • Jacquot S, Kobata T, Iwata S, Morimoto C, Schlossman SF. CD154/CD40 and CD70/CD27 interactions have different and sequential functions in T cell-dependent B cell responses: enhancement of plasma cell differentiation by CD27 signaling. J Immunol. 1997 Sep 15;159(6):2652–2657. [PubMed]
  • Nonoyama S, Shimadzu M, Toru H, Seyama K, Nunoi H, Neubauer M, Yata J, Och HD. Mutations of the CD40 ligand gene in 13 Japanese patients with X-linked hyper-IgM syndrome. Hum Genet. 1997 May;99(5):624–627. [PubMed]
  • Sugita K, Hirose T, Rothstein DM, Donahue C, Schlossman SF, Morimoto C. CD27, a member of the nerve growth factor receptor family, is preferentially expressed on CD45RA+ CD4 T cell clones and involved in distinct immunoregulatory functions. J Immunol. 1992 Nov 15;149(10):3208–3216. [PubMed]
  • Morimoto C, Letvin NL, Distaso JA, Aldrich WR, Schlossman SF. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Güssow D, Rein R, Ginjaar I, Hochstenbach F, Seemann G, Kottman A, Ploegh HL. The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit. J Immunol. 1987 Nov 1;139(9):3132–3138. [PubMed]
  • Korthäuer U, Graf D, Mages HW, Brière F, Padayachee M, Malcolm S, Ugazio AG, Notarangelo LD, Levinsky RJ, Kroczek RA. Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. Nature. 1993 Feb 11;361(6412):539–541. [PubMed]
  • Saiki O, Tanaka T, Wada Y, Uda H, Inoue A, Katada Y, Izeki M, Iwata M, Nunoi H, Matsuda I, et al. Signaling through CD40 rescues IgE but not IgG or IgA secretion in X-linked immunodeficiency with hyper-IgM. J Clin Invest. 1995 Feb;95(2):510–514. [PMC free article] [PubMed]
  • Banchereau J, Bazan F, Blanchard D, Brière F, Galizzi JP, van Kooten C, Liu YJ, Rousset F, Saeland S. The CD40 antigen and its ligand. Annu Rev Immunol. 1994;12:881–922. [PubMed]
  • Müller F, Aukrust P, Nilssen DE, Frøland SS. Reduced serum level of transforming growth factor-beta in patients with IgA deficiency. Clin Immunol Immunopathol. 1995 Aug;76(2):203–208. [PubMed]
  • Durandy A, Schiff C, Bonnefoy JY, Forveille M, Rousset F, Mazzei G, Milili M, Fischer A. Induction by anti-CD40 antibody or soluble CD40 ligand and cytokines of IgG, IgA and IgE production by B cells from patients with X-linked hyper IgM syndrome. Eur J Immunol. 1993 Sep;23(9):2294–2299. [PubMed]
  • Fuleihan R, Ramesh N, Loh R, Jabara H, Rosen RS, Chatila T, Fu SM, Stamenkovic I, Geha RS. Defective expression of the CD40 ligand in X chromosome-linked immunoglobulin deficiency with normal or elevated IgM. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2170–2173. [PMC free article] [PubMed]
  • Foy TM, Durie FH, Noelle RJ. The expansive role of CD40 and its ligand, gp39, in immunity. Semin Immunol. 1994 Oct;6(5):259–266. [PubMed]
  • Durandy A, Hivroz C, Mazerolles F, Schiff C, Bernard F, Jouanguy E, Revy P, DiSanto JP, Gauchat JF, Bonnefoy JY, et al. Abnormal CD40-mediated activation pathway in B lymphocytes from patients with hyper-IgM syndrome and normal CD40 ligand expression. J Immunol. 1997 Mar 15;158(6):2576–2584. [PubMed]
  • Durandy A, Schiff C, Bonnefoy JY, Forveille M, Rousset F, Mazzei G, Milili M, Fischer A. Induction by anti-CD40 antibody or soluble CD40 ligand and cytokines of IgG, IgA and IgE production by B cells from patients with X-linked hyper IgM syndrome. Eur J Immunol. 1993 Sep;23(9):2294–2299. [PubMed]
  • Callard RE, Smith SH, Herbert J, Morgan G, Padayachee M, Lederman S, Chess L, Kroczek RA, Fanslow WC, Armitage RJ. CD40 ligand (CD40L) expression and B cell function in agammaglobulinemia with normal or elevated levels of IgM (HIM). Comparison of X-linked, autosomal recessive, and non-X-linked forms of the disease, and obligate carriers. J Immunol. 1994 Oct 1;153(7):3295–3306. [PubMed]
  • Splawski JB, Jelinek DF, Lipsky PE. Delineation of the functional capacity of human neonatal lymphocytes. J Clin Invest. 1991 Feb;87(2):545–553. [PMC free article] [PubMed]
  • Nonoyama S, Penix LA, Edwards CP, Lewis DB, Ito S, Aruffo A, Wilson CB, Ochs HD. Diminished expression of CD40 ligand by activated neonatal T cells. J Clin Invest. 1995 Jan;95(1):66–75. [PMC free article] [PubMed]
  • Fuleihan R, Ahern D, Geha RS. Decreased expression of the ligand for CD40 in newborn lymphocytes. Eur J Immunol. 1994 Aug;24(8):1925–1928. [PubMed]
  • Splawski JB, Nishioka J, Nishioka Y, Lipsky PE. CD40 ligand is expressed and functional on activated neonatal T cells. J Immunol. 1996 Jan 1;156(1):119–127. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...