CD80 Expression on B Cells Regulates Murine T Follicular Helper Development, Germinal Center B Cell Survival, and Plasma Cell Generation

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2012 Mar 28

PMID 22450810

Citations 64

Authors

Kim L Good-Jacobson

Eunice Song

Shannon Anderson

Arlene H Sharpe

Mark J Shlomchik

Affiliations

Soon will be listed here.

Abstract

Germinal center (GC) B cells and T follicular helper (T(FH)) cells interact in the production of high-affinity long-lived plasma cells (PCs) and memory B cells, although the mechanisms regulating the formation of these long-lived populations remain unclear. Because CD80 is one of the few markers shared by human and murine memory B cells, we investigated its role in the development of GCs, memory cells, and PCs. In CD80-deficient mice, fewer long-lived PCs were generated upon immunization compared with that in B6 controls. In concert, the absence of CD80 resulted in an increase in apoptotic GC B cells during the contraction phase of the GC. CD80(-/-) mice had fewer T(FH) cells compared with that of B6, and residual T(FH) cells failed to mature, with decreased ICOS and PD-1 expression and decreased synthesis of IL-21 mRNA. Mixed bone marrow chimeras demonstrated a B cell-intrinsic requirement for CD80 expression for normal T(FH) cell and PC development. Therefore, B cell expression of CD80 plays a critical role in regulating B-T interactions in both early and late GC responses. This, in turn, results in impaired ability to produce long-lived PCs. These data provide new insights into the development of GCs and Ab-forming cells and the functions of CD80 in humoral immunity.

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References

Freeman G, Borriello F, Hodes R, Reiser H, Hathcock K, Laszlo G . Uncovering of functional alternative CTLA-4 counter-receptor in B7-deficient mice. Science. 1993; 262(5135):907-9. DOI: 10.1126/science.7694362. View

Anderson S, Tomayko M, Ahuja A, Haberman A, Shlomchik M . New markers for murine memory B cells that define mutated and unmutated subsets. J Exp Med. 2007; 204(9):2103-14. PMC: 2118690. DOI: 10.1084/jem.20062571. View

Ozaki K, Spolski R, Feng C, Qi C, Cheng J, Sher A . A critical role for IL-21 in regulating immunoglobulin production. Science. 2002; 298(5598):1630-4. DOI: 10.1126/science.1077002. View

Allen C, Okada T, Tang H, Cyster J . Imaging of germinal center selection events during affinity maturation. Science. 2006; 315(5811):528-31. DOI: 10.1126/science.1136736. View

Hamel K, Cao Y, Wang Y, Rodeghero R, Kobezda T, Chen L . B7-H1 expression on non-B and non-T cells promotes distinct effects on T- and B-cell responses in autoimmune arthritis. Eur J Immunol. 2010; 40(11):3117-27. PMC: 3638795. DOI: 10.1002/eji.201040690. View

Moser K, Tokoyoda K, Radbruch A, MacLennan I, Manz R . Stromal niches, plasma cell differentiation and survival. Curr Opin Immunol. 2006; 18(3):265-70. DOI: 10.1016/j.coi.2006.03.004. View

Takahashi Y, Ohta H, Takemori T . Fas is required for clonal selection in germinal centers and the subsequent establishment of the memory B cell repertoire. Immunity. 2001; 14(2):181-92. DOI: 10.1016/s1074-7613(01)00100-5. View

Jacob J, Przylepa J, Miller C, Kelsoe G . In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells. J Exp Med. 1993; 178(4):1293-307. PMC: 2191212. DOI: 10.1084/jem.178.4.1293. View

Dogan I, Bertocci B, Vilmont V, Delbos F, Megret J, Storck S . Multiple layers of B cell memory with different effector functions. Nat Immunol. 2009; 10(12):1292-9. DOI: 10.1038/ni.1814. View

10.

Yusuf I, Kageyama R, Monticelli L, Johnston R, DiToro D, Hansen K . Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150). J Immunol. 2010; 185(1):190-202. PMC: 2913439. DOI: 10.4049/jimmunol.0903505. View

11.

Salek-Ardakani S, Choi Y, Rafii-El-Idrissi Benhnia M, Flynn R, Arens R, Shoenberger S . B cell-specific expression of B7-2 is required for follicular Th cell function in response to vaccinia virus. J Immunol. 2011; 186(9):5294-303. PMC: 3089765. DOI: 10.4049/jimmunol.1100406. View

12.

Ahmed R, Gray D . Immunological memory and protective immunity: understanding their relation. Science. 1996; 272(5258):54-60. DOI: 10.1126/science.272.5258.54. View

13.

Zotos D, Coquet J, Zhang Y, Light A, DCosta K, Kallies A . IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism. J Exp Med. 2010; 207(2):365-78. PMC: 2822601. DOI: 10.1084/jem.20091777. View

14.

Bar-Or A, Oliveira E, Anderson D, Krieger J, Duddy M, OConnor K . Immunological memory: contribution of memory B cells expressing costimulatory molecules in the resting state. J Immunol. 2001; 167(10):5669-77. DOI: 10.4049/jimmunol.167.10.5669. View

15.

Takahashi Y, Cerasoli D, Dal Porto J, Shimoda M, Freund R, Fang W . Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-xL transgenic mice. J Exp Med. 1999; 190(3):399-410. PMC: 2195593. DOI: 10.1084/jem.190.3.399. View

16.

Haynes N, Allen C, Lesley R, Ansel K, Killeen N, Cyster J . Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation. J Immunol. 2007; 179(8):5099-108. DOI: 10.4049/jimmunol.179.8.5099. View

17.

Good K, Avery D, Tangye S . Resting human memory B cells are intrinsically programmed for enhanced survival and responsiveness to diverse stimuli compared to naive B cells. J Immunol. 2009; 182(2):890-901. DOI: 10.4049/jimmunol.182.2.890. View

18.

Hannum L, Haberman A, Anderson S, Shlomchik M . Germinal center initiation, variable gene region hypermutation, and mutant B cell selection without detectable immune complexes on follicular dendritic cells. J Exp Med. 2000; 192(7):931-42. PMC: 2193308. DOI: 10.1084/jem.192.7.931. View

19.

Keir M, Butte M, Freeman G, Sharpe A . PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008; 26:677-704. PMC: 10637733. DOI: 10.1146/annurev.immunol.26.021607.090331. View

20.

Anderson S, Khalil A, Uduman M, Hershberg U, Louzoun Y, Haberman A . Taking advantage: high-affinity B cells in the germinal center have lower death rates, but similar rates of division, compared to low-affinity cells. J Immunol. 2009; 183(11):7314-25. PMC: 4106706. DOI: 10.4049/jimmunol.0902452. View