IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling.

Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE levels. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house dust mite (HDM)-induced Th2 cell differentiation and allergic airway inflammation, we showed that IL-6 signaling in allergen-specific T cells was required to prevent Th2 cell differentiation and the subsequent IgE response and allergic inflammation.

GM-CSF production by non-classical monocytes controls antagonistic LPS-driven functions in allergic inflammation.

Lipopolysaccharide (LPS) can either promote or prevent T helper 2 (Th2) cell allergic responses. However, the underlying mechanism remains unknown. We show here that LPS activity switches from pro-pathogenic to protective depending on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by non-classical monocytes.

Impaired Tumor-Necrosis-Factor-α-driven Dendritic Cell Activation Limits Lipopolysaccharide-Induced Protection from Allergic Inflammation in Infants.

Infants have a higher risk of developing allergic asthma than adults. However, the underlying mechanism remains unknown. We show here that sensitization of mice with house-dust mites (HDMs) in the presence of low-dose lipopolysaccharide (LPS) prevented T helper 2 (Th2) cell allergic responses in adult, but not infant, mice.

T-Bet IgM Memory Cells Generate Multi-lineage Effector B Cells.

Immunoglobulin M (IgM) memory cells undergo differentiation in germinal centers following antigen challenge, but the full effector cell potential of these cells is unknown. We monitored the differentiation of enhanced yellow fluorescent protein (eYFP)-labeled CD11c and CD11c T-bet IgM memory cells after their transfer into naive recipient mice. Following challenge infection, many memory cells differentiated into IgM-producing plasmablasts.

CD11c+ T-bet+ memory B cells: Immune maintenance during chronic infection and inflammation?

CD11c+ T-bet+ B cells have now been detected and characterized in different experimental and clinical settings, in both mice and humans. Whether such cells are monolithic, or define subsets of B cells with different functions is not yet known. Our studies have identified CD11c+ IgM+ CD19 splenic IgM memory B cells that appear at approximately three weeks post-ehrlichial infection, and persist indefinitely, during low-level chronic infection.

Early derivation of IgM memory cells and bone marrow plasmablasts.

IgM memory cells are recognized as an important component of B cell memory in mice and humans. Our studies of B cells elicited in response to ehrlichial infection identified a population of CD11c-positive IgM memory cells, and an IgM bone marrow antibody-secreting cell population. The origin of these cells was unknown, although an early T-independent spleen CD11c- and T-bet-positive IgM plasmablast population precedes both, suggesting a linear relationship.

The omentum is a site of protective IgM production during intracellular bacterial infection.

Infection of mice with the bacterium Ehrlichia muris elicits a protective T cell-independent (TI) IgM response mediated primarily by a population of CD11c-expressing plasmablasts in the spleen. Although splenic marginal zone (MZ) B cells are considered to be important for TI responses to blood-borne pathogens, MZ B cells were not responsible for generating plasmablasts in response to Ehrlichia muris. Moreover, antigen-specific serum IgM was decreased only modestly in splenectomized mice and in mice that lacked spleen, lymph nodes, and Peyer's patches (SLP mice).

Reduced B lymphoid kinase (Blk) expression enhances proinflammatory cytokine production and induces nephrosis in C57BL/6-lpr/lpr mice.

BLK, which encodes B lymphoid kinase, was recently identified in genome wide association studies as a susceptibility gene for systemic lupus erythematosus (SLE), and risk alleles mapping to the BLK locus result in reduced gene expression. To determine whether BLK is indeed a bona fide susceptibility gene, we developed an experimental mouse model, namely the Blk+/-.lpr/lpr (Blk+/-.