The basic-helix-loop-helix (bHLH) proteins encoded by the E2A gene are broadly expressed transcription regulators which function through binding to the E-box enhancer sequences. The DNA binding activities of E2A proteins are directly inhibited upon dimerization with the Id1 gene product. It has been shown that disruption of the E2A gene leads to a complete block in B-lymphocyte development and a high frequency of neonatal death. We report here that nearly half of the surviving E2A-null mice develop acute T-cell lymphoma between 3 to 10 months of age. We further show that disruption of the Id1 gene improves the chance of postnatal survival of E2A-null mice, indicating that Id1 is a canonical negative regulator of E2A and that the unbalanced ratio of E2A to Id1 may contribute to the postnatal death of the E2A-null mice. However, the E2A/Id1 double-knockout mice still develop T-cell tumors once they reach the age of 3 months. This result suggests that E2A may be essential for maintaining the homeostasis of T lymphocytes during their constant renewal in adult life.Helix-loop-helix (HLH) proteins belong to a family of transcription factors which play important roles in cell fate determination and cellular differentiation (for reviews, see references 29 and 42). They contain a highly conserved sequence motif known as the basic helix-loop-helix (bHLH) domain. The bHLH motif can be further divided into two subdomains, the HLH domain and an adjacent basic region. The HLH domain, consisting of two amphipathic ␣-helices separated by a loop of amino acid sequence of variable length, is responsible for the dimerization between HLH proteins. The basic region,

Abstract. Mating has been found to be costly for females of some species because of toxic products that males transfer to females in their seminal fluid. Such mating costs seem paradoxical, particularly for species in which females mate more frequently than is necessary to fertilize their eggs. Indeed, some studies suggest that females may benefit from mating more frequently. The effect of male ejaculates on female life span and lifetime fecundity was experimentally tested in the variable field cricket, Gryllus lineaticeps. In field crickets, females will mate repeatedly with a given male and mate with multiple males. Females that were experimentally mated either repeatedly or multiply lived more than 32% longer than singly mated females. In addition, multiply mated females produced 98% more eggs than singly mated females. Because females received only sperm and seminal fluid from males in the experimental matings, these life-span and fecundity benefits may result from beneficial seminal fluid products that males transfer to females during mating. Mating benefits rather than mating costs may be common in many animals, particularly in species where female mate choice has a larger effect on male reproductive success than does the outcome of sperm competition.

The mammalian E2A, HEB, and E2-2 genes encode a unique class of basic helix-loop-helix (bHLH) transcription factors that are evolutionarily conserved and essential for embryonic and postnatal development. While the structural and functional similarities among the gene products are well demonstrated, it is not clear why deletion of E2A, but not HEB or E2-2, leads to a complete arrest in B-lymphocyte development. To understand the molecular basis of the functional specificity between E2A and HEB/E2-2 in mammalian development, we generated and tested a panel of E2A knockin mutations including subtle mutations in the E12 and E47 exons and substitution of both E12 and E47 exons with a human HEB cDNA. We find that the alternatively spliced E12 and E47 bHLH proteins of the E2A gene play similar and additive roles in supporting B lymphopoiesis. Further, we find that HEB driven by the endogenous E2A promoter can functionally replace E2A in supporting B-cell commitment and differentiation toward completion. Finally, the postnatal lethality associated with E2A disruption is fully rescued by the addition of HEB. This study suggests that the functional divergence among E12, E47, and HEB in different cell types is partially defined by the context of gene expression.B lymphocytes in mammals are derived from hematopoietic stem cells (HSC) present in the liver during fetal development and bone marrow in adult life. The same HSC also generate T lymphocytes, erythrocytes, macrophages, and other cell types in blood and the lymphoid organs. Once committed to the B-cell lineage, the HSC follow a stepwise differentiation pathway to become B lymphocytes, which subsequently participate in diverse humoral immune responses. It is not entirely known how and when B-lineage cells are first specified from HSC and how B lymphopoiesis is maintained throughout life.B-lineage development can be divided roughly into three discrete stages: progenitor (pro-B), precursor (pre-B), and mature B-cell stages. Rearrangements of immunoglobulin (Ig) genes initiate at the pro-B stage and proceed to completion at the pre-B stage. Pre-B cells expressing functional but nonselfreactive B-cell receptors are selected for survival and expansion to become mature B cells (18). In addition, B cells at various stages of development express lineage-specific markers, such as B220, CD43, and CD19 surface antigens (9, 19). These lineage markers, combined with the status of Ig rearrangements and expression, establish road signs of normal and abnormal progression of B lymphopoiesis (9).Regulation at the transcriptional level is crucial in each step of B-cell development. Indeed, recent studies have shown that E2A, EBF, Pax5, Ikaros, and several other transcription factors play key roles in the pro-and pre-B stages of development (2,14,29,31,35). Disruption of genes encoding each one of these transcription factors arrests B-cell development at either the pro-or pre-B-cell stage. Since deletion of E2A blocks B-cell development prior to the initiation of Ig gene rearrangement, ...