Metabolic control of B cell immune responses
Introduction
B cells play a pivotal role in adaptive immune responses by performing a variety of functions including the secretion of pathogen-specific antibodies. B cells spend most of their life in a quiescent state recirculating through the blood and lymph. Upon antigen exposure and after receiving T cell help, B cells initiate the formation of germinal centers (GC) [1]. During the GC reaction random mutations are introduced into immunoglobulin genes to diversify the B cell antigen receptor (BCR) repertoire. To avoid the emergence of low affinity or autoreactive clones, GC B cells are poised to undergo apoptosis and can only survive if they receive pro-survival signals through the interaction with other cells such as follicular helper T cells. This interaction takes place in the so-called ‘light zone’ of the GC. After an affinity-based selection, GC B cells enter the ‘dark zone’ to undergo clonal expansion. The final output of the GC reaction is the differentiation of GC B cells to long-lived memory B cells or antibody secreting plasma cells. The functional diversity of B cell subsets is reflected by high plasticity of their metabolic profile. Naive B cells are metabolically quiescent and require low levels of catabolic metabolism to sustain energy homeostasis. Following activation, B cells re-shape their metabolic program to meet the energetic and biosynthetic demands of proliferation [2]. This article presents a brief review of recent findings made in the field of B cell metabolism and the insight they provide into the regulation of the humoral immune response.
Section snippets
Metabolic reprogramming in B cells
The primary source of energy and carbon for lymphocytes is glucose; however, other carbohydrates, fatty acids or amino acids can also be metabolized. Glucose can be used to fuel two major metabolic pathways in order to generate energy (Figure 1). During glycolysis, glucose is catabolized to pyruvate, which is further fermented to lactate and secreted. This process yields two molecules adenosine triphosphate (ATP) per molecule glucose. Alternatively, pyruvate can be converted into Acetyl-CoA to
The metabolic environment shapes B cell fate
The metabolic profile of B cells not only reflects the cells’ activation and differentiation status, but also depends on the environment and the cells’ access to nutrients and oxygen. Several examples now exist which illustrate that physiologically relevant changes in the surrounding micro-environment of B cells can skew their development, survival and function. B cells can be exposed to hypoxia within the GC [4,24,25] but also at other sites such as the bone marrow [26,27] or inflamed tissue [
Conclusions
The metabolic state of a B cell is the result of a complex array of inputs including the differentiation and activation status of the cell, nutrient accessibility and other environmental cues. Intracellularly, metabolite-based and protein-based signaling pathways cooperate to instruct cell fate decisions. In the last few years considerable progress has been made towards understanding how various intracellular signaling pathways drive the transition between different metabolic states. In
Conflict of interest statement
Nothing declared.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
J.J was supported by the Ministry of Science, Research and the Arts Baden-Wuerttemberg and the European Social Fund through a Margarete von Wrangell fellowship. Her research is funded by the German Research Foundation (DFG) under Germany‘s Excellence Strategy (CIBSS-EXC-2189_Project ID 390939984 and BIOSS-EXC 294) and by the TRR130 (TP-25).
I would like to gratefully acknowledge a critical reading of the manuscript draft by Ellen J. McAllister.
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