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Lymphocytes exit lymph nodes and return to the bloodstream through the efferent lymphatics. Cyster and colleagues show that lymphocytes exit into cortical sinuses by a pathway dependent on sphingosine 1-phosphate receptor type 1.

Cyster and colleagues show that CD97–CD55 interactions, which trigger Gα₁₃–ARHGEF–Rho cytoskeletal signaling, are needed for proper MZ B cell positioning/retention in the spleen and for optimal antibody responses to T cell-independent antigens.

The molecular mechanisms that govern B cell progenitor localization in bone marrow sinusoids are not understood. Cyster and colleagues demonstrate involvement of cannabinoid receptor 2 in retaining developing B cells in sinusoids.

Defective thymic egress in mice is associated with the peripheral T cell deficiency (Ptcd) locus. Cyster and colleagues find that the actin regulator coronin 1A is mutant in Ptcd and in an atypical patient with SCID.

Immune complexes are captured from lymph by subcapsular macrophages. Cyster and colleagues show that an intricate relay shuttles antigen into germinal centers to drive affinity maturation.

The environmental cues involved in regulating germinal center size are not fully understood. Cyster and colleagues show that the sphingosine 1-phosphate receptor S1P₂ controls the survival and localization of B cells in germinal centers by antagonizing signaling by the kinase Akt and follicular chemoattractants.

The developmental requirements of IL-17-committed γδ T cells remain unclear. Cyster and colleagues show that the transcription factor Sox13 is selectively required for the development of the Vγ4⁺ subset of γδ T cells.

Generation of memory B cells is crucial for protective immunity to infectious agents. Cyster and colleagues show that the transcription factor Hhex interacting with Tle3 promotes memory B cell generation.

The closely related oxysterols, 25-hydroxycholesterol and 7α,25-dihydroxycholesterol, have important functions in innate and adaptive immune responses, ranging from antiviral and inflammation-regulatory effects to a role as a guidance cue for B cells and dendritic cells.

A number of orphan GPCRs show high constitutive activity. Here, the authors show that the high basal activity of some receptors can be explained by their sensitivity to naturally abundant lipids or by penetration of ECL2 in the orthosteric binding pocket.

B cells migrate to the outer or centre lymphoid follicle at different stages of antibody responses. Here it is shown that activated B cells must downregulate the orphan G protein-coupled receptor EBI2 to migrate to the centre follicles, where they mount T dependent antibody responses and establish germinal centres.

S-geranylgeranyl-l-glutathione (GGG) is identified as a cell signalling molecule that interacts with the receptor P2RY8 to mediate migration inhibition and growth regulation of germinal-centre B cells.

Reboldi and colleagues show that high-cholesterol diets influence IgA secretion. Cholesterol-derived metabolites act on plasma cell GPR183 receptors to alter cell positioning of IgA⁺ plasma cells within the lamina propria and suppress antibody responses to intestinal pathogens.

Marginal zone B cells may steal the limelight as the roles of Pyk-2 and BLyS begin to be elucidated. Pyk-2 deficiency leads to their loss whereas signaling via the BLyS receptor may augment their function.

Inactivation of the S1PR2–Gα13–ARHGEF1 signalling pathway in mice allows Akt activation and promotes dissemination of germinal centre B cells, consistent with a role of function-disrupting mutations in the systemic dissemination of diffuse large B-cell lymphoma.

The differentiation of T follicular helper cells requires the G-protein-coupled receptor Ebi2 as well as the interaction with CD25-producing dendritic cells that quench T-cell-derived interleukin-2.

Of 12 serology assays tested, four detect antibodies in more than 80% of patients with COVID-19.

Lymphocyte migration in the spleen is visualized live in mice using a real-time two-photon laser-scanning microscopy approach revealing that marginal zone and follicular B cells are highly motile and can shuttle between compartments, and integrin adhesion is the key to cellular retention in the marginal zone.

High-affinity and isotype-switched antibodies arise from germinal center reactions. Goodnow and colleagues identify the Rho guanine nucleotide–exchange factor DOCK8 as being essential for sustained B cell immune synapse formation in germinal centers and mature antibody responses.

Here, a combination of genetic studies of gene expression, cross-species network analysis and genome-wide association studies has been used to identify gene networks and the loci underlying their regulation in rats. The results show that an inflammatory network driven by interferon regulatory factor 7 contributes to susceptibility to type 1 diabetes, and implicate the innate viral-response pathway and macrophages in the aetiology of this disease.

Distinct subsets of fibroblasts, which differ in their expression of thymus cell antigen 1 (THY1), are responsible for inflammation and tissue damage in mouse models of arthritis.

Memory B cells are critically important for the formation of protective immunity following infection or vaccination, and a better understanding of these cells may inform strategies to overcome hurdles in the development of effective vaccines. This Review discusses the signals and transcription factors that regulate the development and function of germinal centre-derived memory B cells.