Increased Frequency of Pre-germinal Center B Cells and Plasma Cell Precursors in the Blood of Children with Systemic Lupus Erythematosus

Arce, Edsel; Jackson, Deborah G.; Gill, Michelle A.; Bennett, Lynda; Banchereau, Jacques; Pascual, Virginia

doi:10.4049/jimmunol.167.4.2361

Cited by 240 publications

(236 citation statements)

References 61 publications

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“…In addition, the frequency of CD27 + cells was higher in SLE B cells following long-term stimulation. These observations are in agreement with previous studies on SLE reporting higher frequencies of CD27 + blood B cells and plasma cells (Arce et al 2001;Jacobi et al 2003;Odendahl et al 2000), which could be prone to rapid differentiation into Ig-secreting cells through Fig. 3.…”

Section: Discussionsupporting

confidence: 93%

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

Néron

Boire

Dussault

et al. 2009

Arch. Immunol. Ther. Exp.

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Introduction: Aberrant signaling within and between B and T cells, considered to be central in systemic lupus erythematosus (SLE), could depend on enhanced CD40-CD154 activation. As a result, autoreactive B cells, normally anergic, differentiate and secrete antibodies attacking several normal tissues. Thus restorating B cell homeostasis might help control this disease. In this study, two facets of SLE B cells were investigated, namely their in vitro response to CD40-CD154 and the effect of treatment with human immunoglobulins for intravenous use (IVIg). Materials and Methods: Blood samples from SLE patients and healthy volunteers were obtained and used to isolate B cells, which were activated through CD40 in the presence or absence of IVIg. The phenotype, proliferation, and differentiation of the SLE B cells were determined and compared with those of control B cells using flow cytometry and standard ELISA. Results: In this model, CD40-activated SLE B cells, as control B cells, proliferated and differentiated and were characterized by the emergence of CD19 lo CD38 ++ CD138 + CD27 ++ cells. IVIg treatment of the CD40-activated SLE B cells resulted in higher differentiation, characterized by increased secretion rates of IgG and IgM, as reported previously for control B cells. Conclusions: Taken as a whole, such accelerated differentiation of CD40-activated B cells suggests that IVIg may participate in re-equilibration of the antibody repertoire by replacing pathological antibodies by de novo harmless antibodies.

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Section: Discussionsupporting

confidence: 93%

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

Néron

Boire

Dussault

et al. 2009

Arch. Immunol. Ther. Exp.

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“…8A), as previously reported (47)(48)(49). In individual normal donors, Fc␥RIIb expression on memory B lymphocytes appeared to be up-regulated relative to naive B lymphocytes (Fig.…”

Section: Fc␥riib Expression Is Dysregulated On B Lymphocytes In Activsupporting

confidence: 87%

Expression Profile of FcγRIIb on Leukocytes and Its Dysregulation in Systemic Lupus Erythematosus

Yang

et al. 2007

The Journal of Immunology

166

150

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FcγRIIb (CD32B, Online Mendelian Inheritance in Man 604590), an IgG FcR with a tyrosine-based inhibitory motif, plays a critical role in the balance of tolerance and autoimmunity in murine models. However, the high degree of homology between FcγRIIb and FcγRIIa in humans and the lack of specific Abs to differentiate them have hampered study of the normal expression profile of FcγRIIb and its potential dysregulation in autoimmune diseases such as systemic lupus erythematosus (SLE). Using our newly developed anti-FcγRIIb mAb 4F5 which does not react with FcγRIIa, we found that FcγRIIb is expressed on the cell surface of circulating B lymphocytes, monocytes, neutrophils, myeloid dendritic cells (DCs), and at very low levels on plasmacytoid DCs from some donors. Normal donors with the less frequent 2B.4 promoter haplotype have higher FcγRIIb expression on monocytes, neutrophils, and myeloid DCs similar to that reported for B lymphocytes, indicating that FcγRIIb expression on both myeloid and lymphoid cells is regulated by the naturally occurring regulatory single nucleotide polymorphisms in the FCGR2B promoter. FcγRIIb expression in normal controls is up-regulated on memory B lymphocytes compared with naive B lymphocytes. In contrast, in active SLE, FcγRIIb is significantly down-regulated on both memory and plasma B lymphocytes compared with naive and memory/plasma B lymphocytes from normals. Similar down-regulation of FcγRIIb on myeloid-lineage cells in SLE was not seen. Our studies demonstrate the constitutive regulation of FcγRIIb by natural gene polymorphisms and the acquired dysregulation in SLE autoimmunity, which may identify opportunities for using this receptor as a therapeutic target.

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“…Prosurvival effects may also be associated with the dysregulated overproduction of stimulatory factors, such as interferon-␣ (40), which is currently believed to contribute to the accelerated B cell differentiation into plasma cells seen in pediatric lupus patients (41). Similarly, tumor necrosis factor ␣ and stem cell-derived growth factor 1 may play somewhat similar roles in supporting the erosive synovitis of RA (42,43).…”

Section: Mechanisms Of Autoimmunity and Rituximabmentioning

confidence: 99%

Rituximab therapy and autoimmune disorders: Prospects for anti–B cell therapy

Silverman¹,

Weisman²

2003

Arthritis & Rheumatism

344

204

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Increased Frequency of Pre-germinal Center B Cells and Plasma Cell Precursors in the Blood of Children with Systemic Lupus Erythematosus

Cited by 240 publications

References 61 publications

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

Expression Profile of FcγRIIb on Leukocytes and Its Dysregulation in Systemic Lupus Erythematosus

Rituximab therapy and autoimmune disorders: Prospects for anti–B cell therapy

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