B Cell Receptor Signaling in Human Systemic Lupus Erythematosus

Aimee E. Pugh-Bernard; John C. Cambier

Disclosures

Curr Opin Rheumatol. 2006;18(5):451-455. 

In This Article

Altered Distribution of Peripheral B Cell Subsets in Systemic Lupus Erythematosus

Active SLE is linked to B cell lymphopenia and significant alterations in peripheral blood B cell subsets that appear integral to the pathogenesis of disease and not solely caused by therapeutic intervention.[1,2,3,4,5] Naïve peripheral blood B cells (CD19+IgD+CD27-) are more highly depleted than memory B cells (CD19+IgD-CD27+) leading to an uncharacteristic predominance of CD27+ memory B cells.[1,2] This selective depletion of naïve B cells could be resolved by the finding that SLE IgG VH4.34 antibodies have been found to target a developmentally regulated B220-specific glycoform of CD45[2] that is an N-linked N-acetyllactosamine (NAL) determinant expressed on naïve B cells and sterically masked on memory B cells.[6] VH4.34 antibodies are intrinsically autoreactive against the NAL determinant of the blood group I/i antigens, which is structurally similar to the B220-specific glycoform of CD45 found on naïve B cells.[7] VH4.34-encoded antibodies were found in the late 1990s to be cytotoxic.[8,9] While this finding may (partially) explain the depletion of naïve B cells in active disease and suggest that naïve B lymphopenia is secondary to disease, it does not explain the observed decrease in memory B cells. It is also important to note that the majority of SLE patients show an increase in VH4.34 antibodies in their sera during active disease and as a result this is thought to be a clinical indicator of active disease.[2,10]

Expansion of a pregerminal center B cell subset has also been seen in children with SLE.[3] The pregerminal center cells are thought to parallel the germinal center founder cells found within human tonsil.[11] In this study the authors showed that this population is the predominant blood B cell subset in pediatric patients with SLE. The same group described a three-fold expansion of a plasma cell precursor subset (CD20- CD19+/low CD27+/++ CD38++) in the peripheral blood of pediatric patients with SLE, regardless of disease activity. In healthy individuals, the frequency of plasma cells or plasma cell precursors in the peripheral blood is extremely low. Additional groups have observed increased numbers of plasma cell precursors or phenotypically fully mature plasma cells (CD27++, CD38++, CD138+) in the peripheral blood of patients with active disease.[1,3,5,12] As an example of the magnitude of the increase of peripheral blood plasma cells found, one group showed that the mean frequency of CD27++ peripheral blood plasma cells in SLE patients with active disease is 26 ± 15% (range of 7.4-43.1%) compared to 6 ± 4% (range of 1.9-11.2%) in patients with inactive disease.[1] The latter is comparable to levels seen in the peripheral blood of healthy individuals.

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