Spontaneous immunoglobulin-producing capacity of cultures from lupus patients and normal donors following depletion of cells expressing CD19 or CD38

Abstract

SUMMARYCells spontaneously secreting IgG or IgM (ISC) are present at a high level in the blood of patients with systemic lupus erythematosus (SLE). By use of magnetic-bead techniques, mononuclear cells from such patients and healthy donors were fractionated according to expression of CD19 or CD38 and the cell fractions were then cultured in the absence of added mitogen/antigen for 5/6 days. Supernatant IgG and IgM were determined and, in addition, in the CD38 experiments ISC were enumerated both before and after culture. Much of the immunoglobulin-producing capacity of unfractionated cells (UFC) from both donor groups was recovered in the CD19 ¹ fraction, and no immunoglobulin was produced by CD19 þ cells suggesting, unexpectedly, that ISC were not expressing CD19. By contrast, CD38 fractionation resulted in nearly all ISC passing to the CD38 þ fraction which produced levels of immunoglobulin approaching 50% that of UFC. On culture of CD38 ¹ cells there was a build up in the number of IgG and IgM ISC, this being particularly striking in the controls with numbers well in excess of those in UFC. Not all these new ISC became CD38 þ , but the maturation process was more efficient in the SLE patients. The possibility is discussed that the spontaneous response in the CD38 ¹ populations is due to removal of CD38 þ natural killer (NK) cells. Removal of ISC that are present preculture is a helpful initial step in studying ISC generation in the disease.

Perturbations of peripheral B lymphocyte homoeostasis in children with systemic lupus erythematosus

“…With regard to B lymphocytes, spontaneously activated B cells and polyclonal production of Ig including autoantibodies have been repeatedly demonstrated in the peripheral blood and in the bone marrow in SLE. [17][18][19][20][21] The identification of an expansion of peripheral plasma blasts is consistent with these previous findings.…”

Abnormal germinal center reactions in systemic lupus erythematosus demonstrated by blockade of CD154-CD40 interactions

“…Previous studies have defined B cell subsets from inflamed secondary lymphoid tissue such as tonsil (5,(15)(16)(17)(18)(19) or the periphery of active-SLE patients (22)(23)(24)(25)(26) by expression of IgD and CD38. Of note, the current results confirm published studies that have demonstrated that B cells in the periphery of active-SLE patients express significantly higher levels of CD38 than B cells in the periphery of normal, non-autoimmune individuals (22,25,26).…”

“…Following activation in an antigen-and MHC-restricted manner, CD154-expressing T cells initiate the GC reaction by engaging CD40-expressing pre-switch IgD + or postswitch IgD -B cells, thereby inducing them to express early-activation markers (CD69 and CD154) and differentiation markers (CD38, CD5, and CD27) (5)(6)(7)(8)(9)(10) and to proliferate rapidly to form IgD + primary or IgDsecondary follicles, more commonly referred to as GCs (11). Previous studies have defined functional B cell subsets from inflamed secondary lymphoid tissue, such as tonsil (12)(13)(14)(15)(16)(17)(18)(19)(20)(21), or the periphery of active-SLE patients (22)(23)(24)(25)(26)(27)(28)(29) by expression of CD27 and CD5, as well as IgD and CD38. Specifically, B cells that are bright for CD38, CD27, or CD5 have been shown to be Ig-secreting plasma cells, and cells expressing a low level of CD38, CD27, or CD5 have been shown to be memory-cell intermediates in the differentiation pathway to Ig-secreting plasma cells.…”

A tolerogenic peptide down‐regulates mature B cells in bone marrow of lupus‐afflicted mice by inhibition of interleukin‐7, leading to apoptosis

“…The consequence of genetic dysregulation of B‐cell development might be the survival of aberrant B cells. In accordance, it was shown that peripheral B cells taken from SLE patients contain populations that spontaneously produce immunoglobulins and that they can mature into antibody‐secreting cells when cultured in vitro even in the absence of B‐cell differentiation activators 32 . We demonstrated here that the expanded mature B‐cell population in the BM of SLE‐afflicted mice is decreased following treatment with hCDR1, at least because of increased apoptosis of the cells, in which the expression of the death receptor, Fas, was up‐regulated, and the expression of the survival gene, Bcl‐xL, was down‐regulated (Fig.…”