Evidence for an upper affinity threshold for anti-IgM-induced apoptosis in a human B-cell lymphoma.

The influence of ligand:receptor affinity on B-cell antigen receptor (BCR)-induced apoptosis in the IgM+ Burkitt lymphoma line, Ramos, was evaluated with a group of affinity-diverse murine monoclonal antibodies (MoAbs) specific for human B-cell IgM. The studies showed not only a minimal affinity threshold for the induction of apoptosis, but, interestingly, also a maximal affinity threshold above which increases in affinity were associated with diminished apoptosis. The lesser capacity of high-affinity MoAb to induce apoptosis was paralleled by a lesser capacity to induce receptor cross-linking.

Membrane IgM-stimulated human B lymphocytes succumb to activation-related apoptosis at a G1-->S transition: influence of ligand affinity and valency.

Culture of human B lymphocytes with polyclonally activating surrogates for type II T-cell-independent antigen, i.e., anti-IgM mAb and anti-IgM:dextran, resulted in both membrane IgM (mIgM)-triggered S/G2/M entry and apoptosis.

The affinity threshold for human B cell activation via the antigen receptor complex is reduced upon co-ligation of the antigen receptor with CD21 (CR2).

The present studies have examined whether the potential of an Ag to co-ligate the complement (C3d)-binding CD21 receptor complex with the membrane IgM (mIgM) receptor complex can reduce the mIgM:Ag affinity threshold for triggering human B cell S phase entry. A series of Ab:dextran conjugates consisting of affinity-diverse anti-IgM mAb, with and without anti-CD21 mAb, were synthesized as polyclonally reactive, moderately multivalent ligands that mimic C3d-bearing and non-C3d-bearing Ag. Co-ligation of mIgM and CD21 significantly diminished both the ligand concentration threshold and the IgM:ligand affinity threshold for eliciting S phase entry in the presence of IL-4.

Brucella abortus conjugated with a peptide derived from the V3 loop of human immunodeficiency virus (HIV) type 1 induces HIV-specific cytotoxic T-cell responses in normal and in CD4+ cell-depleted BALB/c mice.

We have previously shown that immunization of mice with human immunodeficiency virus (HIV)-derived proteins or peptides conjugated to inactivated Brucella abortus induces the secretion of virus-neutralizing antibodies, predominantly of the immunoglobulin G2a (IgG2a) isotype. In addition, B. abortus activates human CD4+ and CD8+ cells to secrete gamma interferon.