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ILC2s are critical in the immune response to helminths, the development of allergies and homeostasis of adipose tissue. This study demonstrates that the metabolic sensor PPARγ is central for ILC2s activation, proliferation and function in lung and adipose tissue.

Immature B cells expressing self-reactive BCRs induce anergy programs to promote tolerance. Busslinger and colleagues show that the transcription factor Ikaros enforces anergy by inducing transcription of negative-feedback regulators of the BCR and TLR–MyD88 pathways.

B cell development requires interleukin 7 signals that activate the transcription factor STAT5. Busslinger and colleagues report that STAT5 has a permissive rather than instructive role in pro-B cell survival and immunoglobulin recombination.

Microglia clearance activity in adult brain is regulated epigenetically and region-specifically to match neuronal attrition rates. Uncoupling this activity from neural apoptosis leads to aberrant microglia activation & neurodegenerative-like changes.

Pax5 regulates contraction of the immunoglobulin heavy chain (Igh) locus—an essential step in V(D)J recombination—by promoting chromatin loop extrusion via repression of Wapl expression.

By use of a degron-mediated acute protein degradation model, Schwickert and colleagues are able to distinguish between direct and indirect gene targets of multiple transcription factors involved in early B cell development.

The transcription factor Ikaros is required for lymphopoiesis. Busslinger and colleagues show Ikaros positively regulates genes encoding pre-BCR signal transducers and thereby promotes pro-B to pre-B cell progression and proliferation.

B-1a B cells are a distinct subset of mature B cells that provide innate-like protection against pathogens. Busslinger and colleagues identify the transcription factor Bhlhe41 as being essential for B-1a development and self-renewal.

Blimp-1 is known to act as a transcriptional repressor by suppressing genes associated with mature and activated germinal center B cells. Busslinger and colleagues show that Blimp-1 can also directly activate gene expression in plasma cells, including those encoding proteins that regulate the production of membrane-bound immunoglobulin versus secreted immunoglobulin.

Regulatory T cells can adopt specialized differentiation programs in the periphery. Kallies and co-workers show that IRF4 and Blimp-1 control the acquisition of regulatory T cell effector functions, such as IL-10 production.

The transcription factor Blimp-1 is required for the differentiation of activated B cells into plasmablasts. Nutt and colleagues show that plasma cells need Blimp-1 to maintain antibody production by regulating the kinase mTOR and unfolded-protein-response pathways.

V gene recombination at the immunoglobulin heavy chain locus (Igh) is facilitated by extended loop extrusion. In this study, the authors find that, unlike Igh, the κ light chain locus does not involve extended loop extrusion but instead involves multiple, short-range loops for V gene combination.

The transcription factor IRF8 is essential for classical type 1 dendritic cell (cDC1) development. Murphy and colleagues investigate in detail the molecular control of cDC1 fate specification by systematically unpicking the IRF8 enhancer regions.

Immunoglobulin gene rearrangements occur in an organized, temporal way. Skok and colleagues show that immunoglobulin alleles 'pair' to coordinate cleavage and allelic availability.

Although GATA-3 is expressed in hematopoietic stem cells, its function there remains unclear. Iscove and colleagues show that GATA-3 inhibits the self-renewal potential of long-term hematopoietic stem cells downstream of p38 signaling.

B cells and follicular helper T cells in B cell follicles can act as important reservoirs for chronic infection by viruses such as HIV or EBV. Yu and colleagues show that a specialized subpopulation of cytotoxic T cells can enter the B cell follicles to eliminate such virus-infected cells.

Pax5 is a transcription factor important for B cell differentiation and function. Deletion of Pax5 in mature B cells causes them to de-differentiate to less differentiated progenitor cells that can give rise to T cells, demonstrating an unanticipated degree of developmental plasticity in this lineage.

Tetrahydrobiopterin (BH4) is an enzyme co-factor that is involved in the nervous system; it is shown here to also function in T cell activation and proliferation, with roles in autoimmunity, allergic inflammation and cancer.

Massively parallel but cost-effective testing is essential to monitor the spread of pathogenic agents. Here the authors present SARSseq, which uses a dual indexing strategy in a multiplexed RT-PCR reaction to diagnose SARS-CoV-2 at scale.