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Interactions between B and T cells are essential for most antibody responses, but the dynamics of these interactions are poorly understood. By two-photon microscopy of intact lymph nodes, we show that upon exposure to antigen, B cells migrate with directional preference toward the B-zone-T-zone boundary in a CCR7-dependent manner, through a region that(More)
In these studies, IFN gamma-inducing factor (IGIF), unlike IL-12, did not drive Th1 development in BALB/c or C57BL/6 mice, but like IL-1alpha, potentiated IL-12-driven Th1 development in BALB/c mice. IGIF and IL-12 synergized for IFN gamma production from Th1 cells. Unlike IL-1alpha, IGIF had no effect on Th2 cells. IGIF signaled through IRAK, IL-1(More)
Two different approaches to follow clones of B lymphocytes in a diverse preimmune repertoire reveal a new process for eliminating self-reactive cells in the periphery which depends on competition between cells with different specificities. A key feature of this censoring mechanism is the selective exclusion of self-antigen-binding B cells from the normal(More)
Type 1 diabetes and other organ-specific autoimmune diseases often cluster together in human families and in congenic strains of NOD (nonobese diabetic) mice, but the inherited immunoregulatory defects responsible for these diseases are unknown. Here we track the fate of high avidity CD4 T cells recognizing a self-antigen expressed in pancreatic islet beta(More)
In transgenic mice, self-reactive B lymphocytes are eliminated if they encounter membrane-bound self antigens during their development within the bone marrow. We show here that two separate and sequential events, arrested development and cell death, bring about B cell elimination. Developmental arrest is an early outcome of antigen binding in immature B(More)
The long-standing hypothesis that tolerance to self antigens is mediated by either elimination or functional inactivation (anergy) or self-reactive lymphocytes is now accepted, but little is known about the factors responsible for initiating one process rather than the other. In the B-cell lineage, tolerant self-reactive cells persist in the peripheral(More)
Transgenic mice carrying a rearranged Ig gene encoding the H chain of a lysozyme-specific antibody were used to examine the effect of antigen binding affinity on elimination of self-reactive B cells. In H chain transgenic mice, B cells expressed surface IgM and IgD composed of lysozyme-specific H chains and many different possible L chains from endogenous L(More)
The development of Th1- or Th2-type responses determines the type of immune response that is elicited in response to Ag. Responsiveness to IL-12 is critical for the development of Th1-type CD4+ T cells required for cell-mediated immune responses. Addition of IL-12 to primary cultures of CD4+ T cells stimulated with OVA and splenocytes or dendritic cells(More)
A series of immunoglobulin (Ig)-transgenic mice were generated to study the functional capabilities of the IgM and IgD classes of B lymphocyte antigen receptor in regulating both cellular development and responses to specific antigen. B cells from Ig-transgenic mice expressing either hen-egg lysozyme (HEL)-specific IgM or IgD alone were compared with B(More)