Immature and mature antibodies as defenders against cancer

Antibodies(Abs)are glycoprotein molecules that represent an essential component of the adaptative immune response.They are secreted in body fluids and act as a critical part of immune defense.Although recognition of self-antigens by Abs is normally selected against during B-cell development,autoreactive Abs can be generated as a result of pathological immune responses,as observed in autoimmune diseases.Autoantibodies can also be produced in cancer patients,where they may have beneficial roles[1].Indeed,the presence of intratumoral antibody-secreting cells(ASCs)and B-cell-rich tertiary lymphoid structures(TLSs)has been observed in many cancer types and generally correlates with a favorable clinical prognosis[2,3,4,5,6].The existence of specific antitumor antibody responses suggests that tumor cells express molecules that are recognized as nonself antigens by the immune system or that tolerance of self-antigens expressed on cancer cells is lost[1,4].The study of the origin of tumor-reactive Abs and their specificity and functions is of paramount importance for understanding the development of adaptive antitumor immune responses and for revealing novel therapeutic avenues.A recent publication in Cell by Mazor et al.[7]has provided an important advance in our understanding of antibody responses in cancer.In particular,this work paves the way for the distinction between antibody-reactive tumors and antibody-nonreactive tumors,which is reminiscent of the dichotomy of the noninfiltrated“cold”tumor microenvironment(TME)in contrast with the highly infiltrated with immune cells“hot”TME[8].Moreover,an important finding of the study was the demonstration that tumor-directed autoreactivity may be either preexisting or induced by somatic hypermutations,a mechanism related to the chronicity of cancer.

Microbial symphony orchestrated by mucosal IgA

The ability of an organism to handle the beauty and cruelty of existence is largely due to a complex network of molecular and cellular interactions and processes named the immune system.Important components of this network are antibodies(Abs)that have key roles in immune defense and regulation.Typical biological functions of Abs include neutralizing pathogens by blocking functionally important molecules and/or to eliciting lethal effector functions by bridging the recognition of pathogens with binding to different innate immune receptors.

Noncanonical antibody strategy for broad and potent neutralization of influenza virus

Pathogens with high levels of genetic variability,such as HIV-1 and influenza virus,evade the immune system by constantly changing their proteins vulnerable to neutralization by antibodies Consequently,these highly evolvable viruses are notoriously elusive targets for vaccines.In rare cases,infection of humans with HIV-1 or influenza virus results in production of antibodies that can neutralize a very broad spectrum of viral strains.Such antibodies are referred to as broadly neutralizing.

Anti-IgE IgG autoantibodies isolated from therapeutic normal IgG intravenous immunoglobulin induce basophil activation

Basophils are rare granulocytes.Despite representing only~0.5%of all leukocytes,basophils have several important physiological functions.1,2 Although basophils lack the classic features of professional antigen-presenting cells,3–7 through the secretion of cytokines,they orient the immune response by polarizing Th2 differentiation and supporting B-cell differentiation and class switching.Basophils are also critical for mediating protection against helminth infection.1,2,8,9 Basophils receive activation signals from diverse sources.It is well recognized that cytokines such as IL-3,granulocyte–macrophage colony-stimulating factor(GM-CSF),thymic stromal lymphopoietin(TSLP)and IL-33;various toll-like receptor ligands;allergen-bound IgE provide activation signals to basophils and induce the release of inflammatory mediators.10–15 In addition,several reports have also demonstrated the existence of anti-IgE autoantibodies that possess the capacity to induce basophil activation in patients with chronic spontaneous urticaria(CSU),atopic or non-atopic asthma or autoimmune disease.16–21 However,isolation and functional exploration of such anti-IgE IgG autoantibodies from either healthy donors or patients have not been attempted yet.By using a pooled normal IgG preparation from healthy donors,specifically intravenous immunoglobulin G(IVIG)22 that represents the complete IgG repertoire of a normal individual,we attempted to address this outstanding question in the field.