Differential expression of FCRLA in naïve and activated mouse B cells.

FCRLA is an intracellular B cell protein that belongs to the FcR-like family. Using newly generated FCRLA-specific antibodies, we studied the constitutive expression pattern of mouse FCRLA and monitored changes during an immune response and following in vitro B cell activation. All B cell subpopulations examined expressed FCRLA.

Germinal center reutilization by newly activated B cells.

Germinal centers (GCs) are specialized structures in which B lymphocytes undergo clonal expansion, class switch recombination, somatic hypermutation, and affinity maturation. Although these structures were previously thought to contain a limited number of isolated B cell clones, recent in vivo imaging studies revealed that they are in fact dynamic and appear to be open to their environment. We demonstrate that B cells can colonize heterologous GCs.

Exclusion of natural autoantibody-producing B cells from IgG memory B cell compartment during T cell-dependent immune responses.

In healthy individuals, a substantial proportion of circulating Abs exhibit polyreactivity and self-reactivity. These Abs are referred to as natural autoantibodies (NAAs). As part of the innate immunity, NAAs play an important role in eliminating pathogens.

Initial clonal expansion of germinal center B cells takes place at the perimeter of follicles.

Current models of the germinal center (GC) response propose that after stimulation at the edges of T cell zones, pre-GC B cells directly migrate to the center of follicles and proliferate to form GCs. We followed the interrelationship of proliferation, differentiation, and microenvironmental locale in populations of pre-GC B cells responding to antigen. In contrast to the predictions of current models, after accumulation at the T-B interface, these cells appeared at the perimeter of follicles adjacent to the marginal zone.

Influence of Fas on the regulation of the response of an anti-nuclear antigen B cell clonotype to foreign antigen.

A peripheral B cell tolerance checkpoint appears to be operative during the germinal center (GC) reaction. We previously showed that a transgenic BCR clonotype that is 'dual reactive' for the hapten arsonate (Ars) and nuclear auto-antigens is stimulated to enter the GC response via Ars immunization. However, the participation of this clonotype in this response wanes with time and it gives rise to few memory B cells capable of mounting a secondary anti-Ars IgG response.

Quantitatively reduced participation of anti-nuclear antigen B cells that down-regulate B cell receptor during primary development in the germinal center/memory B cell response to foreign antigen.

The peripheral B cell compartment contains high levels of "polyreactivity" including autospecificities. We have described a pathway that certain autoreactive B cells may take in gaining stable access to the foreign Ag-responsive peripheral compartment. This pathway was revealed in mice expressing a targeted Ig H chain transgene encoding BCRs with "multireactivity" for the hapten arsonate and DNA-based autoantigens.

FcgammaRIIB regulates autoreactive primary antibody-forming cell, but not germinal center B cell, activity.

The low-affinity FcR for IgG FcgammaRIIB suppresses the development of IgG autoantibodies and autoimmune disease in normal individuals, but how this effect is mediated is incompletely understood. To investigate this issue, we created FcgammaRIIB-deficient versions of two previously described targeted BCR-transgenic lines of mice that contain follicular B cells with specificity for the hapten arsonate, but with different levels of antinuclear autoantigen reactivity. The primary development and tolerance of both types of B cells were unaltered by the absence of FcgammaRIIB.

Identification of CD16-2, a novel mouse receptor homologous to CD16/Fc gamma RIII.

It is believed that mouse Fc gamma RIII arose by an evolutionarily recent recombination, which brought together the extracellular domains from Fc gamma RII with the transmembrane/cytoplasmic region from the ancestor Fc gamma RIII. Here, we report identification of a mouse gene encoding a transmembrane receptor that may be regarded as the true ortholog of nonrodent CD16/Fc gamma RIII. Designated CD16-2, the novel protein is highly similar to human Fc gamma RIIIA in the signal peptide (60% identical residues), and in the extracellular domains (65%).

Bcl-2 rescues the germinal center response but does not alter the V gene somatic hypermutation spectrum in MSH2-deficient mice.

Ab V genes in mice deficient for the postreplication mismatch repair factor MutS homolog (MSH2) have been reported to display an abnormal bias for hypermutations at G and C nucleotides and hotspots. We previously showed that the germinal center (GC) response is severely attenuated in MSH2-deficient mice. This suggested that premature death of GC B cells might preclude multiple rounds of hypermutation necessary to generate a normal spectrum of base changes.

A family of highly diverse human and mouse genes structurally links leukocyte FcR, gp42 and PECAM-1.

A group of genes encoding proteins structurally related to the leukocyte Fc receptors (FcRs) and termed the IFGP family was identified in human and mouse. Sequences of four human and two mouse cDNAs predict proteins differing by domain composition. One of the mouse cDNAs encodes a secreted protein, which, in addition to four immunoglobulin (Ig)-like domains, contains a scavenger receptor superfamily-related domain at the C-terminus.

FCRL, a novel member of the leukocyte Fc receptor family possesses unique structural features.

A novel conserved member of the leukocyte Fc receptor (FcR) family was identified in human and mouse. The presumably secreted protein, designated FCRL (FcR-like) is comprised of four domains. The three N-terminal domains are related to the extracellular region of FcgammaRI, with the second (35-37% residue identity) and the third (46-52%) domains showing highest similarity.