Asthma discordance in twins is linked to epigenetic modifications of T cells.

T cells mediate the inflammatory responses observed in asthma among genetically susceptible individuals and have been suspected to be prone to epigenetic regulation. However, these relationships are not well established from past clinical studies that have had limited capacity to control for the effects of variable genetic predisposition and early environmental exposures. Relying on a cohort of monozygotic twins discordant for asthma we sought to determine if epigenetic modifications in T cells were associated with current asthma and explored whether such modifications were associated with second hand smoke exposures.

The in vitro derivation of phenotypically mature and diverse B cells from immature spleen and bone marrow precursors.

The capacity of immature B cells of the spleen and bone marrow to differentiate in vitro into cells representing mature end stage cells was investigated using B-cell activating factor belonging to the TNF family (BAFF) and Notch pathway activators. Immature splenic and bone marrow B cells were found, in the presence of both of these activators, to mature into cells with follicular mature (FM) and marginal zone (MZ) cell phenotypes. Such cells were functionally responsive to B-cell-specific activation.

Regulation of murine splenic B cell CR3 expression by complement component 3.

Complement component C3 has established roles in both innate and adaptive immune responses. C3 cleavage products function in B cell activation through the complement receptors CD21/35. Phenotypes of Ab production between CD21/35(-/-) and C3(-/-) mice are not always congruent, implicating additional roles for C3 in B cell responses.

CD21 signaling via C3 regulates Purkinje cell protein 4 expression.

Complement receptor proteins CR2 (CD21) and CR1 (CD35) have been identified as components of the murine B cell co-receptor complex. Gene expression profiles between naïve WT, C3-/-, and CD21/35-/- B cells demonstrate enhanced expression of a Ca(2+)-modulating gene, Pcp4, in WT mice compared to the complement-deficient animals. Increased expression of Pcp4 is also coincident with B cell maturation into end stage phenotypes.

Comparative functional evolution of human and mouse CR1 and CR2.

The complement cascade is regulated by a series of proteins that inhibit complement convertase activity. These regulatory proteins, most of which possess binding sites for C3b and/or C4b, can be roughly divided into two groups, one that controls inappropriate complement convertase activity on the surface of cells, and another that controls convertase activity on immune complexes in serum. In this review we focus upon the structural and functional comparisons of the CR1 and CR2 proteins of man and mouse.

Complement receptors 1 and 2 influence the immune environment in a B cell receptor-independent manner.

The CD21/35 proteins are complement receptors implicated in controlling and interpreting activation states of the innate and acquired immune responses. One defect of CD21/35(-/-) animals is depressed production of Ag-specific IgG3 which we show is evident in vivo but not in vitro. Gene expression profiles obtained from naive wild-type and CD21/35(-/-) splenocytes demonstrated enhanced expression of inflammatory mediators from CD11b(+) splenocytes in the CD21/35(-/-) animals.

Mice lacking CD21 and CD35 proteins mount effective immune responses against Borrelia burgdorferi infection.

CD21/35(-/-) mice, deficient in CD21 and CD35 (complement receptors 2 and 1, respectively), were infected with Borrelia burgdorferi to assess the role of these receptors in a chronic bacterial infection. Although CD21/35(-/-) mice on both C57BL/6 and BALB/c backgrounds produced less B. burgdorferi-specific antibodies than did wild-type mice, spirochete levels and arthritis severity were similar.

Cysteine-rich domains of muc3 intestinal mucin promote cell migration, inhibit apoptosis, and accelerate wound healing.

Background & Aims: Muc3 intestinal mucin contains an extracellular cysteine-rich domain with 2 epidermal growth factor (EGF)-like motifs. The aim of this study was to determine the functional properties of Muc3 proteins.

Methods: Glutathione S-transferase-fusion proteins containing both Muc3 EGF-like domains (m3EGF1,2) or truncated versions (m3EGF1 and m3EGF2) were purified from Escherichia coli.