Dysfunctional B cells in systemic lupus erythematosus
Section snippets
Characteristics of B lymphocytes
Intriguing new insights into the multiform influences of B lymphocytes on surrounding cells have been unravelled over the past decade. They are involved in shaping lymphoid white pulp architecture, including the formation of follicular dendritic cells (DC). They also coordinate T lymphocytes and influence the pattern of immune responses through the production of cytokines both in T cells and DCs (Fig. 1).
Overactivity of B cells in systemic diseases
SLE is characterized by auto-Ab to a large assortment of nuclear Ags, including double-stranded DNA and widely expressed intracellular components, such as extractable nuclear Ags. Not long ago, evidence has been provided [22] that intracellular Ags positively select B cells to differentiate into IgM auto-Ab-secreting plasma cells. Consistent with this propensity to yield auto-Ab, B cells from patients with active SLE express activation markers, most notably CD154. Such a phenotype reflects an
Dysfunction of B cells in autoimmunity
The reasons for the selection of autoreactive B cells during development remain a subject of debate. This could be due to a defect in negative selection, resulting in aberrant survival. Altered longevity enables autoreactive B cells to escape the screening process before entry into secondary lymphoid organs (SLO) and within the GCs, due to excessive expression of Bcl-2, which is an antiapoptotic factor, or mutations in the gene of the death-inducing receptor Fas (Table 2).
References (36)
- et al.
The mosaic of autoimmunity
Immunol. Today
(1989) - et al.
Distinct roles in lymphoid organogenesis for lymphotoxins alpha and beta revealed in lymphotoxin beta-deficient mice
Immunity
(1997) - et al.
The expanding universe of T-cell subsets: Th1, Th2 and more
Immunol. Today
(1996) - et al.
OX-40: life beyond the effector T cell stage
Semin. Immunol.
(1998) - et al.
Systemic lupus erythematosus
Lancet
(2001) T cell in the pathogenesis of systemic lupus erythematosus
Front. Biosci.
(2001)- et al.
Development of follicular dendritic cells in lymph nodes of B-cell-depleted mice
Cell Tissue Res.
(1998) - et al.
Host origin of follicular dendritic cells induced in the spleen of SCID mice after transfer of allogeneic lymphocytes
Immunology
(1995) - et al.
Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response
J. Exp. Med.
(1996) - et al.
Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin
Science
(1994)
Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling
J. Exp. Med.
The sequential role of lymphotoxin and B cells in the development of splenic follicles
J. Exp. Med.
The CD40 antigen and its ligand
Annu. Rev. Immunol.
Limited role of CD28-mediated signals in T helper subset differentiation
J. Exp. Med.
Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T–T help via APC activation
J. Exp. Med.
Role of OX40 signals in coordinating CD4 T cell selection, migration, and cytokine differentiation in T helper (Th)1 and Th2 cells
J. Exp. Med.
CD4 T cell cytokine differentiation: the B cell activation molecule, OX40 ligand, instructs CD4 T cells to express interleukin 4 and upregulates expression of the chemokine receptor, Blr-1
J. Exp. Med.
B cells solicit their own help from T cells
J. Exp. Med.
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