Regulation of IL-4 responsiveness in lymphoma B cells

Abstract

Abstract-The responsiveness to IL-4 with and without costimulation with anti-IgM antibodies or phorbolester was studied in 35 cases of low grade non-Hodgkin Iymphoma by analyzing enhancement of CD23 and HLA dass li expression. The predominant phenotype responds directly to IL-4. Separate differentiation states can be distinguished according to coordinate or differential upregulation of CD23 and HLA dass II molecules by IL-4 alone, and differences in responsiveness to anti-IgM antibodies. A particular subgroup of B-lymphoma cells defines a separate stage of B-eeil differentiation. They fail to express high affinity binding sites for IL-4 and accordingly do not respond to IL-4-mediated signals. Cross-linking membrane lgM receptors or direct activation of protein kinase C via phorbolester induces IL-4 receptor expression and subsequent IL-4 reactivity.

Persistent polyclonal B-cell lymphocytosis - an important differential diagnosis of B-cell chronic lymphocytic leukemia

“…In contrast to normal peripheral B cells and also B-CLL cells [27], the in vitro tests showed no response of PPBL-cells to IL-4 as assayed by induction of CD23 and HLA-DR expression. Also co-stimulation with F2m antibodies, which regularly induces IL-4 receptors on normal B-lymphocytes and co-stimulates with IL-4 for enhanced CD23 expression [27], failed in PPBL cells (Fig.…”

“…Whereas F2m antibodies enhanced HLA-DR expression on these cells, they failed to co-stimulate IL-4-mediated CD23 expression and induction of in vitro proliferation. In contrast, normal B cells respond to F2m in both assays, whereas B-CLL cells usually do not respond to surface IgM crosslinking by anti-IgM antibodies at all [27].…”

“…Also co-stimulation with F2m antibodies, which regularly induces IL-4 receptors on normal B-lymphocytes and co-stimulates with IL-4 for enhanced CD23 expression [27], failed in PPBL cells (Fig. 3a, b).…”

Inhibition of T cell/B cell interaction by B-CLL cells

“…IL-4 alone was a good inducer of CD23 on normal B cells, whereas IL-4 mediated CD23 expression on B-CLL was usually quite modest. 11,26 However, costimulation with CD40 ligand and IL-4 resulted in a strong activation of CD23 expression on normal B lymphocytes and B-CLL ( Figure 5). These experiments show that B-CLL cells, like normal B cells, are able to receive a stimulating signal by CD40L transfected fibroblasts.…”

“…10 Therefore, they can be stimulated by lymphokines or contact-dependent T helper cell signals similar to normal B lymphocytes. [11][12][13][14] T cells, isolated from CLL patients, exhibit normal T-helper cell function in respect of cytokine secretion and proliferative responses after polyclonal activation. 15 The predominance of B cells as accessory cells, however, apparently alters the immune function of T helper cells in vitro, resulting in an enhanced secretion of interleukin-2, whereas interferon-␥ was only slightly induced and IL-4 was not expressed.…”